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CitationGPTv2_test

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CitationGPTRetr11400

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: New criteria for Alzheimer disease and mild cognitive impairment: implications for the practicing clinician. Abstract of the paper: BACKGROUND In most research studies and clinical trials, Alzheimer disease (AD) has been diagnosed using the criteria developed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association work group in 1984. Developments over the last 27 years have lead to the need for new diagnostic criteria. REVIEW SUMMARY Four articles in the journal Alzheimer's & Dementia in 2011 describe new criteria for AD dementia and mild cognitive impairment (MCI) due to the AD pathophysiological process (MCI due to AD) and the underlying rationale for them. These new criteria emphasize that the AD pathophysiological process starts years and perhaps decades before clinical symptoms, and that biomarkers can be used to detect amyloid β deposition and the effects of neurodegeneration in the brain. CONCLUSIONS These new criteria are immediately helpful to the practicing clinician, providing more accurate and specific guidelines for the diagnosis of AD dementia and MCI due to AD. As new diagnostic tools and new treatments for AD become available, diagnosis using these criteria will enable patients with this disorder to receive the best possible care.

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CitationGPTRetr11401

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: New diagnostic criteria for Alzheimer's disease and mild cognitive impairment for the practical neurologist. Abstract of the paper: Four articles in the journal Alzheimer's and Dementia in 2011 describe new criteria for Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI) due to the AD pathophysiological process (MCI due to AD), as well as the underlying rationale for them. The new criteria also include preclinical AD criteria but these are intended purely for research purposes. The new criteria emphasise that the AD pathophysiological process starts years and perhaps decades before clinical symptoms, and that biomarkers can detect amyloid β deposition and the effects of neurodegeneration in the brain. The criteria are recommendations based upon consensus meetings and will require future validation. Nonetheless, the authors believe that they are immediately helpful to the practising clinician, providing more accurate and specific guidelines for the diagnosis of AD dementia and MCI due to AD. As new diagnostic tools and treatments for AD become available, diagnoses using these criteria will enable patients with AD dementia, MCI due to AD and eventually preclinical AD to receive the best possible care.

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CitationGPTRetr11402

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Abstract of the paper: The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.

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CitationGPTRetr11403

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: [Proposal of criteria for clinical diagnosis of mild cognitive impairment, dementia and Alzheimer's disease]. Abstract of the paper: The most widely accepted criteria for Alzheimer's disease (AD) diagnosis (NINCDS-ADRDA and DSM-IV) do not allow to differentiate accurately between AD and other degenerative dementias which have recently formulated criteria for its clinical diagnosis. Therefore, it is necessary to bring AD diagnostic criteria up to date in order to optimise their specificity, by assessing its most specific clinical manifestations, its most representative markers and those features typical of other diseases which are usually taken into account for a differential diagnosis. According to the latest reports on the subject, the disturbances suffered by memory, behaviour and the rest of cognitive and executive functions must be equally considered when establishing the syndromic diagnosis of dementia; this will always require the coexistence of an evident functional impairment. Due to this, the concepts of "dementia" and "mild cognitive impairment" should be clearly distinguished. For the time being, AD can only be diagnosed when dementia has been proved and this shows a series of cognitive, behavioural and neurological features which are representative of it. Nevertheless, some diagnostic markers appear to be precocious and specific enough to try to identify those patients who suffer from mild cognitive impairment due to an incipient stage of AD. We are suggesting some criteria for the clinical diagnosis of dementia, mild cognitive impairment and AD that seem to be more detail

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CitationGPTRetr11404

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Cognitive deficits and clinical diagnosis of Alzheimer's disease. Abstract of the paper: We used cognitive deficits detected by neuropsychological testing to evaluate clinical diagnosis of Alzheimer's disease. Deficits were defined with respect to performance of control subjects according to procedural guidelines set by a NINCDS-ADRDA Work Group. The most frequent deficits were in recent memory and lexical-semantic language abilities. Clinical diagnosis of Alzheimer's disease was compared with diagnosis based on a criterion of two or more cognitive deficits both on initial neuropsychological testing and on testing repeated a year later in some subjects. Initial clinical diagnosis identified 96% of cases who met the criterion when first tested and 100% of those with multiple deficits at follow-up. Specificity with respect to the criterion was 86% on initial testing and 89% at follow-up. These findings support the validity of clinical diagnosis of Alzheimer's disease using the NINCDS-ADRDA criteria.

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CitationGPTRetr11405

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease. Abstract of the paper: At the end of the activity, participants will be able to:Implement evidence-based methods for cognitive impairment screening in primary care. Identify correct diagnostic criteria for mild cognitive impairment (MCI) and Alzheimer disease (AD) based on current guideline recommendations. Design appropriate and effective treatment plans for patients with MCI and AD and refer to a specialist when necessary. Describe advances in testing and treatment for AD that may impact dementia care.

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CitationGPTRetr11406

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Mild cognitive impairment. Abstract of the paper: PURPOSE OF REVIEW The term mild cognitive impairment (MCI) is used to describe older subjects with demonstrable cognitive impairment who have not crossed the threshold for dementia. Because patients with MCI have an increased risk of developing dementia, especially Alzheimer disease (AD), there is significant interest in the clinical characterization of these subjects and in understanding the pathophysiology of the transition from MCI to AD. RECENT FINDINGS The MCI syndrome, as an expression of an incipient disorder that may lead to dementia, is extremely heterogeneous and may coexist with systemic, neurologic, or psychiatric disorders that can cause cognitive deficits. Recent clinical criteria were designed to take into account the different forms of clinical presentation of the syndrome, and introduced the possible contribution of biomarkers to the clinical diagnosis. Bedside diagnosis of MCI can be difficult, since patients who report having cognitive problems may have normal scores in global cognitive scales or in brief neuropsychological instruments. SUMMARY This article presents the evolution of the clinical concept of MCI, the operationalization of its current definitions, the development of biomarkers that can help to identify an underlying neurodegenerative process as the etiology of the syndrome, and its proposed treatments.

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CitationGPTRetr11407

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Current concepts of mild cognitive impairment and their applicability to persons at-risk for familial Alzheimer's disease. Abstract of the paper: The definition of mild cognitive impairment (MCI) as a precursor for Alzheimer's disease (AD) represented an important step forward in diagnosing the illness in its earliest stage. However, diagnoses based principally on cognitive performance have limitations in that there is variability between centers in which tests are employed and in how they are interpreted. Advances in our understanding of imaging and biochemical changes occurring early in the illness have improved our ability to diagnose AD in this early phase and diagnostic criteria for AD have been proposed recently based on such biomarkers. Persons inheriting autosomal dominant mutations causing familial AD (FAD) are essentially certain to develop the disease. In our studies of preclinical persons at-risk for inheriting FAD, we applied MCI diagnostic criteria to carriers of FAD mutations to ascertain the extent to which they identified persons in the earliest stages of the clinical illness. Our results indicate the relative prevalence of MCI subtypes varies considerably depending on the tests used to measure cognition. Furthermore, we found that cognitive complaints in such persons were less predictive of mutation status than were informants' reports of cognitive loss. The study of FAD provides an opportunity to test various criteria for early AD and these observations should be taken into consideration in future iterations of such diagnostic criteria.

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CitationGPTRetr11408

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Definitions of dementia and predementia states in Alzheimer's disease and vascular cognitive impairment: consensus from the Canadian conference on diagnosis of dementia. Abstract of the paper: There have been several newly proposed sets of diagnostic criteria for Alzheimer's disease/mild cognitive impairment, advanced by the National Institute of Aging/Alzheimer's Association working groups in 2011 and by the International Working Group in 2007 and 2010. These sets each aim to provide broader disease stage coverage with incorporation of disease biomarkers into the diagnostic process. They have focused particular attention on the earlier identification of disease with focus on the preclinical and predementia stages. This paper reviews these diagnostic criteria and provides 2012 consensus recommendations from the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia on their applications in both clinical and research settings.

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CitationGPTRetr11409

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Towards an earlier diagnosis of Alzheimer disease (Proceedings of the 5th MCI Symposium, 2007). Abstract of the paper: The 5th annual Mild Cognitive Impairment Symposium, held on April 13th and 14th, 2007, in Miami Beach, Florida, focused on the question of whether the time has come to revise criteria for Alzheimer disease (AD). The symposium, sponsored by the Wien Center for Alzheimer's Disease and Memory Disorders, Mt Sinai Medical Center in Miami Beach, Florida; and the Byrd Alzheimer Center and Research Institute in Tampa, Florida, brought together an international group of clinicians and researchers to examine current evidence for developing new criteria for AD and for outlining areas that still require clarification. Neuropathologic, neuroimaging, epidemiologic, and clinical perspectives were presented and discussed, as well as the impact of ethnic and cultural differences. As became evident, each perspective introduces different challenges in terms of selecting the appropriate assessment tools; determining when, where, and by whom the diagnosis should be given; and deciding whether multiple sets of criteria are needed for use in different settings, for example, research versus primary care practices. As was intended, the symposium delivered no consensus; however, there was substantial support for the idea that AD can and probably should be diagnosed before the onset of dementia, particularly as new interventions become available.

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CitationGPTRetr11410

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Alzheimer's disease: the problem of incorrect clinical diagnosis. Abstract of the paper: We reviewed the medical records of eight patients clinically diagnosed with Alzheimer's disease who were found on autopsy to have neuropathologic findings inconsistent with Alzheimer's disease. The clinical criteria for the diagnosis of probable Alzheimer's disease from the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) were retrospectively applied to these patients. The patients presented with clinical features atypical for Alzheimer's disease early in the course of the disease, including focal neurologic findings, gait abnormalities, motor speech abnormalities, and extrapyramidal features. Attention to these clinical red flags may decrease the likelihood of misdiagnosis of Alzheimer's disease in a patient with a non-Alzheimer's disease cause of dementia.

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CitationGPTRetr11411

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Abstract of the paper: Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.

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CitationGPTRetr11412

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Mild Cognitive Impairment in Geriatrics. Abstract of the paper: Mild cognitive impairment remains a clinical diagnosis, aided by history, neurologic examination, screening mental status examination, and secondary testing. It can be difficult to distinguish from normal aging without understanding a patient's prior level of intellectual function and new complaint. Geriatricians encounter patients with mild cognitive impairment in all long-term care settings. Making the diagnosis allows patients and their families to understand limits and develop strategies to maximize function. Etiologies associated with mild cognitive impairment include degenerative and vascular processes, psychiatric causes, and comorbid medical conditions. Treatable medical conditions may also present as mild cognitive impairment and have reversible outcomes.

False

CitationGPTRetr11413

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Clinical diagnosis and management of Alzheimer's disease. Abstract of the paper: The diagnosis of dementia of the Alzheimer's type is defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and the National Institute of Neurologic, Communicative Disorders and Stroke-AD and Related Disorders Association. The latter divides diagnosis into definite, probable, and possible Alzheimer's disease (AD), with definitive diagnosis requiring pathologic confirmation. Both criteria require that other causes of dementia are excluded. A diagnosis of AD can be made with reasonably high accuracy using a combination of clinical criteria, neuropsychologic testing, and conventional CT and MR imaging. There is increasing emphasis on early recognition. Although current therapies produce a mild improvement in symptoms, there are several disease-modifying therapies on the horizon. This article reviews current standards in clinical diagnosis and management.

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CitationGPTRetr11414

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Abstract of the paper: The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid beta as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.

True

CitationGPTRetr11415

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Mild cognitive impairment: narrative review of taxonomies and systematic review of their prediction of incident Alzheimer's disease dementia. Abstract of the paper: Early detection of Alzheimer's disease is vital for developing novel treatments. Attempts to identify the intermediate state between normal cognition and dementia have evolved over the past 50 years. Current taxonomies of mild cognitive impairment (MCI) may be criticised for their imprecise operationalisation. With the advent of biomarkers such as amyloid-beta positron emission tomography imaging in established Alzheimer's disease, much research has focused on establishing which factors predict progression from MCI to Alzheimer's disease dementia. In this review, we discuss the historical context of MCI before reviewing the literature of MCI subtypes and their risk of progression to Alzheimer's disease dementia. Finally, we summarise the literature and discuss limitations and weaknesses of how the construct is operationalised and implemented, before offering suggestions for development of the concept of MCI. We conclude that MCI must be empirically defined for the sake of its predictive validity to identify Alzheimer's disease before dementia develops.

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CitationGPTRetr11416

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Mild cognitive impairment: believe it or not? Abstract of the paper: Mild cognitive impairment (MCI) was previously defined as a transitional state that can precede dementia, but the condition and the rates of conversion remain controversial. MCI is now the focus of natural history studies, along with Alzheimer's disease (AD) prevention. The objective of our review will be to consider the question of whether MCI is a well enough established entity that it can be a diagnosis in medical practice and a valid target of Alzheimer's prevention therapy. MCI was originally defined by Petersen et al. (1999) as progressive memory loss, prodrome of Alzheimer's disease. More recently MCI has been expanded to other cognitive domains with other potential causes like normal aging, fronto-temporal dementia, and vascular dementia. Despite many consensus conferences, experts cannot agree on critical aspects of the MCI, particularly with respect to its clinical utility. Based on neuropsychological studies, a hippocampal memory profile has been proposed for MCI as prodromal AD. Further research is needed to advance these criteria. We have no doubt, however, that in the future, the diagnosis of AD as disease (not only a dementia syndrome) will be made in the early pre-dementia stage and will be drawn from a combination of neuropsychological, neuro-imaging and CSF biomarkers.

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CitationGPTRetr11417

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Mild Cognitive Impairment in Clinical Practice: A Review Article. Abstract of the paper: The spectrum of cognitive decline in the elderly ranges from what can be classified as normal cognitive decline with aging to subjective cognitive impairment to mild cognitive impairment (MCI) to dementia. This article reviewed the up-to-date evidence of MCI including the diagnostic criteria of MCI due to Alzheimer's disease, vascular cognitive impairment and MCI due to Parkinson disease, management and preventive intervention of MCI. There are various etiologies of MCI, and a large number of studies have been conducted to ascertain the practical modalities of preserving cognition in predementia stages. Lifestyle modification, such as aerobic exercise, is an approved modality to preserve cognitive ability and decrease the rate of progression to dementia, as well as being recommended for frailty prevention.

False

CitationGPTRetr11418

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: Parkinson's and Alzheimer's diseases: Focus on mild cognitive impairment. Abstract of the paper: The mild cognitive impairment (MCI) concept was developed to identify the earliest stages of cognitive impairment. MCI and, more specifically, amnestic MCI were initially proposed as transitional states that ultimately progress to full blown Alzheimer's disease (AD). However, MCI subjects do not uniformly progress to dementia (either AD or another) and may revert back to normal cognitive state. The MCI as concept has been borrowed from AD to other neurodegenerative diseases, particularly Parkinson's disease (PD). However the operational definition of MCI may not adequately convey the intended concept. Additional modifications to the concept and its operationalization are needed in order to better identify patients with incipient cognitive impairment and to guide clinical and research practices. Patients with PD have a very high likelihood of developing dementia, insidiously over many years. Cognitive impairment may start even before other symptoms. No constellation of cognitive symptoms in an otherwise healthy individual will herald development of AD or indeed will progress to dementia, including PD-dementia, in high likelihood. At present, identification of subtle cognitive dysfunction even in a person with diagnosed PD does not benefit the patient and should be avoided, except for research purposes.

False

CitationGPTRetr11419

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad was diagnosed according to dsmiv criteria and mci according to modifications of petersens criteria Title of the paper: New clinical criteria for the Alzheimer's disease spectrum. Abstract of the paper: New criteria for diagnosing Alzheimer's disease (AD) were recently published. These criteria cover the entire spectrum of AD including dementia due to AD, mild cognitive impairment due to AD, and preclinical AD. A major feature of the new criteria is that they distinguish between the clinical characteristics of the disorder and the pathological features. Earlier criteria were based on clinical features alone. The new criteria include the use of imaging and other biomarkers to aid in diagnosis. The criteria regarding clinical features are currently being used in practice; the criteria regarding biomarkers still need to be validated.

False

CitationGPTRetr11420

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Monoamine oxidase inhibitors: promising therapeutic agents for Alzheimer's disease (Review). Abstract of the paper: Activated monoamine oxidase (MAO) has a critical role in the pathogenesis of Alzheimer's disease (AD), including the formation of amyloid plaques from amyloid β peptide (Aβ) production and accumulation, formation of neurofibrillary tangles, and cognitive impairment via the destruction of cholinergic neurons and disorder of the cholinergic system. Several studies have indicated that MAO inhibitors improve cognitive deficits and reverse Aβ pathology by modulating proteolytic cleavage of amyloid precursor protein and decreasing Aβ protein fragments. Thus, MAO inhibitors may be considered as promising therapeutic agents for AD.

False

CitationGPTRetr11421

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: A comprehensive review of monoamine oxidase inhibitors as Anti-Alzheimer's disease agents: A review. Abstract of the paper: Monoamine oxidases (MAO-A and MAO-B) are mammalian flavoenzyme, which catalyze the oxidative deamination of several neurotransmitters like norepinephrine, dopamine, tyramine, serotonin, and some other amines. The oxidative deamination produces several harmful side products like ammonia, peroxides, and aldehydes during the biochemical reaction. The concentration of biochemical neurotransmitter alteration in the brain by MAO is directly related with several neurological disorders like Alzheimer's disease and Parkinson's disease (PD). Activated MAO also contributes to the amyloid beta (Aβ) aggregation by two successive cleft β-secretase and γ-secretase of amyloid precursor protein (APP). Additionally, activated MAO is also involved in aggregation of neurofibrillary tangles and cognitive destruction through the cholinergic neuronal damage and disorder of the cholinergic system. MAO inhibition has general anti-Alzheimer's disease effect as a consequence of oxidative stress reduction prompted by MAO enzymes. In this review, we outlined and addressed recent understanding on MAO enzymes such as their structure, physiological function, catalytic mechanism, and possible therapeutic goals in AD. In addition, it also highlights the current development and discovery of potential MAO inhibitors (MAOIs) from various chemical scaffolds.

False

CitationGPTRetr11422

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Targeting beta-amyloid pathogenesis through acetylcholinesterase inhibitors. Abstract of the paper: Although the hallmarks of neurodegeneration in Alzheimer's brains are well known, one of the current difficulties is related to the lack of solid evidence about the ultimate factors that give rise to the pathogenesis of this disease, creating a great challenge for the definition of efficient treatments for Alzheimer's disease (AD). Current therapeutic option for AD patients is the use of acetylcholinesterase (AChE) inhibitors, which gives only a symptomatic relief. However, recent studies show a long-lasting effect in a certain percentage of patients. In fact, there is accumulating evidence that an AChE has secondary non-cholinergic functions including the processing and deposition of beta-amyloid (Abeta). AChE could play a role in the Abeta metabolism and during an early step in the development of the senile plaque, as revealed by the finding that AChE accelerates Abeta deposition. Considering the non-classical AChE functions, their relationships with AD hallmarks, and the putative role of peripheral anionic site in all these functions, the dual binding site AChE inhibitors may acquire importance for AD treatment. On the other hand, the interference of AChE inhibitors with Abeta processing is not a general rule for this class of compounds with the involvement of other features such as chemical structure and/or genetic regulation. This review highlights the collection of several compounds with an outstanding profile against AChE-induced amyloid aggregation and potent AChE inhibitory activity, indicating the possibility of targeting Abeta through the inhibition of AChE and reveals the emergence of a new generation of AChE inhibitors aiming to be excellent candidate drugs for the future cure of Alzheimer's disease.

False

CitationGPTRetr11423

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Alzheimer's disease: redox dysregulation as a common denominator for diverse pathogenic mechanisms. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of dementia and a progressive neurodegeneration that appears to result from multiple pathogenic mechanisms (including protein misfolding/aggregation, involved in both amyloid β-dependent senile plaques and tau-dependent neurofibrillary tangles), metabolic and mitochondrial dysfunction, excitoxicity, calcium handling impairment, glial cell dysfunction, neuroinflammation, and oxidative stress. Oxidative stress, which could be secondary to several of the other pathophysiological mechanisms, appears to be a major determinant of the pathogenesis and progression of AD. The identification of oxidized proteins common for mild cognitive impairment and AD suggests that key oxidation pathways are triggered early and are involved in the initial progression of the neurodegenerative process. Abundant data support that oxidative stress, also considered as a main factor for aging, the major risk factor for AD, can be a common key element capable of articulating the divergent nature of the proposed pathogenic factors. Pathogenic mechanisms influence each other at different levels. Evidence suggests that it will be difficult to define a single-target therapy resulting in the arrest of progression or the improvement of AD deterioration. Since oxidative stress is present from early stages of disease, it appears as one of the main targets to be included in a clinical trial. Exploring the articulation of AD pathogenic mechanisms by oxidative stress will provide clues for better understanding the pathogenesis and progression of this dementing disorder and for the development of effective therapies to treat this disease.

False

CitationGPTRetr11424

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Management of Alzheimer's disease-An insight of the enzymatic and other novel potential targets. Abstract of the paper: Alzheimer's disease (AD) is a well-known cause of memory loss and dementia in elderly people all across the world. It is pathophysiologically characterized by the extracellular deposition of amyloid beta (Aβ) proteins and retention of intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins. Several enzymes, such as lipoxygenases, acetylcholinesterases, secretases, glycogen synthase kinase 3, caspases, sirtuins have been reported to actively participate in the pathogenesis of AD. Due to the limited drug for the management of AD till now (only memantine and four other acetylcholinesterase inhibitors), there is an urgent need to find out the novel inhibitors that could specifically act against these enzymes or therapeutically important targets, and barricade or decelerate AD progression. In this current review, we aim to unravel various enzymes and their potential inhibitors that could be exploited against AD pathogenesis. We have also covered several other important miscellaneous targets which could be used as AD therapeutics.

False

CitationGPTRetr11425

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Antioxidant approaches for the treatment of Alzheimer's disease. Abstract of the paper: Oxidative stress is an important factor, and one that acts in the earliest stages, of Alzheimer's disease (AD) pathogenesis. The reduction of oxidative stress has been tested as a therapy for AD. While the trial of vitamin E supplementation in moderately severe AD is the most promising so far, it also reveals the limitations of general antioxidant therapies that simply lower oxidative stress and, therefore, the complexity of the redox system. The multiple contributing factors that foster the clinical manifestations of AD should be considered when designing antioxidative stress therapy. In this article, we discuss the multiple pathogenic mechanisms of oxidative stress in AD and the potential targeting approaches.

False

CitationGPTRetr11426

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: The role of acetylcholinesterase in the pathogenesis of Alzheimer's disease. Abstract of the paper: Treatment of Alzheimer's disease has been dominated by the use of acetylcholinesterase (AChE) inhibitors. These drugs compensate for the death of cholinergic neurons and offer symptomatic relief by inhibiting acetylcholine (ACh) turnover and restoring synaptic levels of this neurotransmitter. Recently, however, AChE itself has been implicated in the pathogenesis of Alzheimer's disease. In particular, it appears that AChE may directly interact with amyloid-beta in a manner that increases the deposition of this peptide into insoluble plaques. This new role suggests that properly designed AChE inhibitors might be able to act as disease-modifying agents rather than as mere palliatives. Additionally, numerous studies have suggested that cholinergic modulation and other functional consequences of AChE inhibition may affect amyloid precursor protein processing and protect neurons against a variety of insults. It therefore seems likely that new AChE inhibitors, which capitalize on all these strengths would be excellent candidates for future Alzheimer's disease therapy.

False

CitationGPTRetr11427

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Are reactive oxygen species involved in Alzheimer's disease? Abstract of the paper: Alzheimer's disease has a multifactorial pathogenesis. Among the various factors involved, this review examines, in particular, the possibility of oxidative stress, meaning an imbalance between the formation and spread of reactive oxygen species (ROS) and the antioxidant defenses. This theory is supported by the following observations: (a) the alteration of mitochondrial function, which is likely to lead to the electron leakage in the respiratory chain and the consequent formation of superoxide radicals; (b) the unbalanced high activity of superoxide dismutase and monoamine oxidase B which causes the production of more H2O2; (c) the alteration of iron homeostasis which, in combination with the superoxide and H2O2, gives rise to the most deleterious hydroxyl radicals; (d) the increased lipid peroxidation and membrane alterations; (e) the pro-aggregating effect of ROS on beta/A4 protein and the C-terminal fragment of amyloid precursor (A4CT). Most of these changes are already present in the normal aging brain but are aggravated in AD presumably over a number of years. However, further investigations are needed to confirm these theories particularly regarding the alterations of another target of ROS, the proteins. Peroxidative stress is presumably present in the AD brain. This stress might not be a primary factor in the pathogenesis of AD, but a consequence of the tissue injury. In any case, it could contribute considerably to the pathology, in a vicious cycle of actions and reactions resulting in a critical mass of metabolic errors, responsible in the end for this disease.

False

CitationGPTRetr11428

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Monoamine oxidase-B inhibition in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of dementia in late life. There is still no clear-cut consensus whether this disease involves genetic or environmental factors or both. There is a great need to find a way to delay the disease, as delaying the onset of the disease will bring a great relieve on social and medical resources. The monoamine oxidase-B (MAO-B) inhibitors were shown to be effective in treating Parkinson's disease and possibly AD, with concomitant extension of life span. This article gives a short review on MAO-B inhibitors and their mechanism for neuroprotective effects in AD.

False

CitationGPTRetr11429

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer's disease. Abstract of the paper: Accumulating evidence indicates a solid relationship between several enzymes and Alzheimer's disease. Cholinesterases and monoamine oxidases are closely associated with the disease symptomatology and progression and have been tackled simultaneously using several multifunctional ligands. This design strategy offers great chances to alter the course of Alzheimer's disease, in addition to alleviation of the symptoms. More than 15 years of research has led to the identification of various dual cholinesterase/monoamine oxidase inhibitors, while some showing positive outcomes in clinical trials, thus giving rise to additional research efforts in the field. The aim of this review is to provide an update on the novel dual inhibitors identified recently and to shed light on their therapeutic potential.

False

CitationGPTRetr11430

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment. Abstract of the paper: Oxidative stress has been implicated to play a crucial role in the pathogenesis of a number of diseases, including neurodegenerative disorders, cancer, and ischemia, just to name a few. Alzheimer disease (AD) is an age-related neurodegenerative disorder that is recognized as the most common form of dementia. AD is histopathologically characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles, the presence of oligomers of amyloid beta-peptide (Abeta), and synapse loss. In this review we discuss the role of Abeta in the pathogenesis of AD and also the use of redox proteomics to identify oxidatively modified brain proteins in AD and mild cognitive impairment. In addition, redox proteomics studies in in vivo models of AD centered around human Abeta(1-42) are discussed.

False

CitationGPTRetr11431

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a deadly outcome. AD is the leading cause of senile dementia and although the pathogenesis of this disorder is not known, various hypotheses have been developed based on experimental data accumulated since the initial description of this disease by Alois Alzheimer about 90 years ago. Most approaches to explain the pathogenesis of AD focus on its two histopathological hallmarks, the amyloid beta protein- (A(beta)-) loaded senile plaques and the neurofibrillary tangles, which consist of the filament protein tau. Various lines of genetic evidence support a central role of A(beta) in the pathogenesis of AD and an increasing number of studies show that oxidation reactions occur in AD and that A(beta) may be one molecular link between oxidative stress and AD-associated neuronal cell death. A(beta) itself can be neurotoxic and can induce oxidative stress in cultivated neurons. A(beta) is, therefore, one player in the concert of oxidative reactions that challenge neurons besides inflammatory reactions which are also associated with the AD pathology. Consequently, antioxidant approaches for the prevention and therapy of AD are of central interest. Experimental as well as clinical data show that lipophilic antioxidants, such as vitamin E and estrogens, are neuroprotective and may help patients suffering from AD. While an additional intensive elucidation of the cellular and molecular events of neuronal cell death in AD will, ultimately, lead to novel drug targets, various antioxidants are already available for a further exploitation of their preventive and therapeutic potential. reserved

False

CitationGPTRetr11432

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Oxidative stress and the pathogenesis of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia in the elderly. Patients with AD suffer a gradual deterioration of memory and other cognitive functions, which eventually leads to a complete incapacity and death. A complicated array of molecular events has been implicated in the pathogenesis of AD. The major pathological characteristics of AD brains are the presence of senile plaques, neurofibrillary tangles, and neuronal loss. Growing evidence has demonstrated that oxidative stress is an important factor contributing to the initiation and progression of AD. However, the mechanisms that lead to the disruption of redox balance and the sources of free radicals remain elusive. The excessive reactive oxygen species may be generated from mechanisms such as mitochondria dysfunction and/or aberrant accumulation of transition metals, while the abnormal accumulation of Abeta and tau proteins appears to promote the redox imbalance. The resulted oxidative stress has been implicated in Abeta- or tau-induced neurotoxicity. In addition, evidence has suggested that oxidative stress may augment the production and aggregation of Abeta and facilitate the phosphorylation and polymerization of tau, thus forming a vicious cycle that promotes the initiation and progression of AD.

False

CitationGPTRetr11433

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors. Abstract of the paper: Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer's disease (AD). Activated MAO induces the amyloid-beta (Aβ) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme's physiology may lead to the future advancement of these drugs.

False

CitationGPTRetr11434

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: [Oxidative stress and Alzheimer's disease]. Abstract of the paper: INTRODUCTION According to the oxidative stress hypothesis, the pathogenesis of several diseases should be related with an excessive production of prooxidant substances (free radicals, transition metals), the deficiency of antioxidant defensive mechanisms, or both. Oxidative stress has been implicated in the pathogenesis of aging of the brain and several neurological diseases, including Alzheimer's disease (AD). DEVELOPMENT In recent years there are many data suggesting a possible role of oxidative stress in the pathogenesis of AD. These include the demonstration of increased oxidation of lipids, proteins and deoxyribonucleic acid, alterations in mitochondrial function and the possible role of amyloid beta and its precursor protein in the oxidative reactions in experimental models (cortical neuronal cultures and transgenic animals). CONCLUSIONS Many studies show increased oxidative stress in the brain of patients with AD, although its possible role con the pathogenesis of this disease are controversial.

False

CitationGPTRetr11435

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Comprehensive review of mechanisms of pathogenesis involved in Alzheimer's disease and potential therapeutic strategies. Abstract of the paper: AD is a progressive neurodegenerative disorder and a leading cause of dementia in an aging population worldwide. The enormous challenge which AD possesses to global healthcare makes it as urgent as ever for the researchers to develop innovative treatment strategies to fight this disease. An in-depth analysis of the extensive available data associated with the AD is needed for a more comprehensive understanding of underlying molecular mechanisms and pathophysiological pathways associated with the onset and progression of the AD. The currently understood pathological and biochemical manifestations include cholinergic, Aβ, tau, excitotoxicity, oxidative stress, ApoE, CREB signaling pathways, insulin resistance, etc. However, these hypotheses have been criticized with several conflicting reports for their involvement in the disease progression. Several issues need to be addressed such as benefits to cost ratio with cholinesterase therapy, the dilemma of AChE selectivity over BChE, BBB permeability of peptidic BACE-1 inhibitors, hurdles related to the implementation of vaccination and immunization therapy, and clinical failure of candidates related to newly available targets. The present review provides an insight to the different molecular mechanisms involved in the development and progression of the AD and potential therapeutic strategies, enlightening perceptions into structural information of conventional and novel targets along with the successful applications of computational approaches for the design of target-specific inhibitors.

False

CitationGPTRetr11436

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Acetylcholinesterase inhibitors as a starting point towards improved Alzheimer's disease therapeutics. Abstract of the paper: The knowledge about the pathogenesis and the development of the neurodegeneration associated with Alzheimer's disease (AD) has been organised throughout the years into two theories, namely the cholinergic and the amyloid hypotheses. The loss of cholinergic neurotransmission and the abnormal aggregation and deposition of the amyloid-beta peptide (A beta) in the brain are retained as the central events by the two theories, respectively. These phenomena and their pathological consequences are the main targets of the drug discovery strategies based on each hypothesis. However, the two paradigms share some common aspects as shown by several experimental evidences, such that they might even fit into a unifying scenario of neuropathology and neurodegeneration. In this context, in a perspective of drug discovery, the enzyme acetylcholinesterase (AChE) holds a key position, as it is a main target for cholinomimetic AD drugs being responsible for the breakdown of the neurotransmitter, and it is also involved in the aggregation of A beta and the formation of the neurotoxic fibrils. Following this view, in recent years, a drug design strategy has emerged, directed to finding molecules able to inhibit both of these actions exerted by AChE. In this review, we will briefly introduce the biological basis of this strategy, and then will account for the early results obtained in this field in our and in other laboratories. The main focus will be on potential lead compounds for which some experimental evidence exists supporting the hypothesis of their dual action, as AChE inhibitors and blockers of the AChE-induced A beta aggregation.

False

CitationGPTRetr11437

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Oxidant/Antioxidant imbalance and the risk of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia characterized by progressive loss of memory and other cognitive functions among older people. Senile plaques and neurofibrillary tangles are the most hallmarks lesions in the brain of AD in addition to neurons loss. Accumulating evidence has shown that oxidative stress-induced damage may play an important role in the initiation and progression of AD pathogenesis. Redox impairment occurs when there is an imbalance between the production and quenching of free radicals from oxygen species. These reactive oxygen species augment the formation and aggregation of amyloid-β and tau protein hyperphosphorylation and vice versa. Currently, there is no available treatments can modify the disease. However, wide varieties of antioxidants show promise to delay or prevent the symptoms of AD and may help in treating the disease. In this review, the role of oxidative stress in AD pathogenesis and the common used antioxidant therapies for AD will summarize.

False

CitationGPTRetr11438

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Oxidative stress mediates the pathogenic effect of different Alzheimer's disease risk factors. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. Mechanistically, the major cause of the disease bases on the altered processing of the amyloid-beta (Abeta) precursor protein (APP), resulting in the accumulation and aggregation of neurotoxic forms of Abeta. Abeta derives from the sequential proteolytic cleavage of the beta- and gamma-secretases on APP. The causes of Abeta accumulation in the common sporadic form of AD are not completely known, but they are likely to include oxidative stress (OS). OS and Abeta are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta. Moreover, OS produces several effects that may contribute to synaptic function and cell death in AD. We and others have shown that the expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal and that there is a significant correlation between BACE1 activity and oxidative markers in sporadic AD. OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. Thus, our data strengthen the hypothesis that OS is a basic common pathway of Abeta accumulation, common to different AD risk factors.

False

CitationGPTRetr11439

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple factors have been recognized to be implicated in the pathogenesis of ad which provide diverse targets including oxidative stress acetylcholinesterase enzyme ache butyrylcholinesterase bche monoamine oxidase mao amyloidb peptide ab aggregation etc to screen drugs to treat this disease Title of the paper: Target Enzyme in Alzheimer's Disease: Acetylcholinesterase Inhibitors. Abstract of the paper: Alzheimer's Disease (AD), affecting a large population worldwide is characterized by the loss of memory and learning ability in the old population. The enzyme Acetylcholinesterase Enzyme (AChE) is the key enzyme in the hydrolysis of the neurotransmitter acetylcholine and is also the target of most of the clinically used drugs for the treatment of AD but these drugs provide only symptomatic treatment and have the limitation of loss of therapeutic efficacy with time. The development of different strategies targeting the AChE enzyme along with other targets like Butyl Cholinesterase (BChE), amyloid-β (Aβ), β-secretase-1 (BACE), metals antioxidant properties and free radical scavenging capacity has been focused in recent years. Literature search was conducted for the molecules and their rational design which have shown inhibition for AChE and the other abovementioned targets. Several hybrid molecules incorporating the main sub-structures derived from diverse chemotypes like acridine, quinoline, carbamates, and other heterocyclic analogs have shown desired pharmacological activity with a good profile in a single molecule. It is followed by optimization of the activity through structural modifications guided by structure-activity relationship studies. It has led to the discovery of novel molecules 17b, 20, and 23 with desired AChE inhibition along with desirable activity against other abovementioned targets for further pre-clinical studies.

False

CitationGPTRetr11440

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron: the Redox-active center of oxidative stress in Alzheimer disease. Abstract of the paper: Although iron is essential in maintaining the function of the central nervous system, it is a potent source of reactive oxygen species. Excessive iron accumulation occurs in many neurodegenerative diseases including Alzheimer disease (AD), Parkinson's disease, and Creutzfeldt-Jakob disease, raising the possibility that oxidative stress is intimately involved in the neurodegenerative process. AD in particular is associated with accumulation of numerous markers of oxidative stress; moreover, oxidative stress has been shown to precede hallmark neuropathological lesions early in the disease process, and such lesions, once present, further accumulate iron, among other markers of oxidative stress. In this review, we discuss the role of iron in the progression of AD.

True

CitationGPTRetr11441

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: The role of iron as a mediator of oxidative stress in Alzheimer disease. Abstract of the paper: Iron is both essential for maintaining a spectrum of metabolic processes in the central nervous system and elsewhere, and potent source of reactive oxygen species. Redox balance with respect to iron, therefore, may be critical to human neurodegenerative disease but is also in need of better understanding. Alzheimer disease (AD) in particular is associated with accumulation of numerous markers of oxidative stress; moreover, oxidative stress has been shown to precede hallmark neuropathological lesions early in the disease process, and such lesions, once present, further accumulate iron, among other markers of oxidative stress. In this review, we discuss the role of iron in the progression of AD.

False

CitationGPTRetr11442

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. Abstract of the paper: Excess free iron generates oxidative stress that hallmarks diseases of aging. The observation that patients with Alzheimer's disease or Parkinson's disease show a dramatic increase in their brain iron content has opened the possibility that disturbances in brain iron homeostasis may contribute to the pathogenesis of these disorders. While the reason for iron accumulation is unknown, iron localization correlates with the production of reactive oxygen species in those areas of the brain that are prone to neurodegeneration. A role for iron is also proposed in atherosclerosis, a further frequent disorder of aging. We will review experimental evidences for an involvement of iron in these diseases and discuss some mouse models with impairment in iron-related genes that may be useful to study the role of iron in these disorders.

True

CitationGPTRetr11443

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron and neurodegenerative disorders. Abstract of the paper: The brain shares with other organs the need for a constant and readily available supply of iron and has a similar array of proteins available to it for iron transport, storage, and regulation. However, unlike other organs, the brain places demands on iron availability that are regional, cellular, and age sensitive. Failure to meet these demands for iron with an adequate supply in a timely manner can result in persistent neurological and cognitive dysfunction. Consequently, the brain has developed mechanisms to maintain a continuous supply of iron. However, in a number of common neurodegenerative disorders, there appears to be an excess accumulation of iron in the brain that suggests a loss of the homeostatic mechanisms responsible for regulating iron in the brain. These systems are reviewed in this article. As a result of a loss in iron homeostasis, the brain becomes vulnerable to iron-induced oxidative stress. Oxidative stress is a confounding variable in understanding the cell death that may result directly from a specific disease and is a contributing factor to the disease process. The underlying pathogenic event in oxidative stress is cellular iron mismanagement.

False

CitationGPTRetr11444

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron in Alzheimer's Disease: From Physiology to Disease Disabilities. Abstract of the paper: Reactive oxygen species (ROS) play a key role in the neurodegeneration processes. Increased oxidative stress damages lipids, proteins, and nucleic acids in brain tissue, and it is tied to the loss of biometal homeostasis. For this reason, attention has been focused on transition metals involved in several biochemical reactions producing ROS. Even though a bulk of evidence has uncovered the role of metals in the generation of the toxic pathways at the base of Alzheimer's disease (AD), this matter has been sidelined by the advent of the Amyloid Cascade Hypothesis. However, the link between metals and AD has been investigated in the last two decades, focusing on their local accumulation in brain areas known to be critical for AD. Recent evidence revealed a relation between iron and AD, particularly in relation to its capacity to increase the risk of the disease through ferroptosis. In this review, we briefly summarize the major points characterizing the function of iron in our body and highlight why, even though it is essential for our life, we have to monitor its dysfunction, particularly if we want to control our risk of AD.

False

CitationGPTRetr11445

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Oxidative stress and iron imbalance in Alzheimer disease: how rust became the fuss! Abstract of the paper: The role of oxidative stress in the pathogenesis of Alzheimer disease has gone from epiphenomena to phenomena. This transition, from disregarded to accepted theory, started in the early-mid 1990s and was accelerated by a number of reports in the literature showing that redox-active sources of transition metals, such as iron, were increased in the brain at early stages of disease. As such, it became apparent that not only was there damage but, more importantly, the machinery to exact such damage was ever present. In this review, the author chronicles his personal perspective on the past, present, and future of oxidative stress in Alzheimer disease.

False

CitationGPTRetr11446

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron: a pathological mediator of Alzheimer disease? Abstract of the paper: Brains from patients with Alzheimer disease (AD) show a disruption in the metabolism of iron, such that there is an accumulation of iron in senile plaques, and an altered distribution of iron transport and storage proteins. One of the earliest events in AD is the generation of oxidative stress, which may be related to the generation of free radicals by the excess iron that is observed in the disease. Iron has also been shown to mediate the in vitro toxicity of amyloid-beta peptide, and the presence of iron in most in vitro systems could underlie the toxicity that is normally attributed to amyloid-beta in these studies. In contrast, several recent studies have suggested that amyloid-beta may decrease oxidative stress and decrease the toxicity of iron. Continued examination of the complex interactions that occur between iron and amyloid-beta may assist in the elucidation of the mechanisms that underlie the neurodegeneration that leads to dementia in AD.

False

CitationGPTRetr11447

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Overdosing on iron: Elevated iron and degenerative brain disorders. Abstract of the paper: Brain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer's disease and Parkinson's disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.

False

CitationGPTRetr11448

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Brain iron transport and neurodegeneration. Abstract of the paper: Despite years of investigation, it is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders. Also, it is not clear whether iron accumulation in the brain is an initial event that causes neuronal death or is a consequence of the disease process. Here, we propose that iron and iron-induced oxidative stress constitute a common mechanism that is involved in the development of neurodegeneration. Also, we suggest that, at least in some neurodegenerative disorders, brain iron misregulation is an initial cause of neuronal death and that this misregulation might be the result of either genetic or non-genetic factors.

False

CitationGPTRetr11449

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron, brain ageing and neurodegenerative disorders. Abstract of the paper: There is increasing evidence that iron is involved in the mechanisms that underlie many neurodegenerative diseases. Conditions such as neuroferritinopathy and Friedreich ataxia are associated with mutations in genes that encode proteins that are involved in iron metabolism, and as the brain ages, iron accumulates in regions that are affected by Alzheimer's disease and Parkinson's disease. High concentrations of reactive iron can increase oxidative-stress induced neuronal vulnerability, and iron accumulation might increase the toxicity of environmental or endogenous toxins. By studying the accumulation and cellular distribution of iron during ageing, we should be able to increase our understanding of these neurodegenerative disorders and develop new therapeutic strategies.

False

CitationGPTRetr11450

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Brain iron metabolism and neurodegenerative disorders. Abstract of the paper: Iron, an essential element for central nervous system (CNS) function, has frequently been found to accumulate in brain regions that undergo degeneration in neurological diseases such as Alzheimer disease, Parkinson disease, Friedreich ataxia and other disorders. However, the precise role of iron in the cause of many neurodegenerative diseases is unclear. To assist in understanding the potential importance of iron in CNS disease, this review summarizes the present knowledge in the areas of CNS iron metabolism, homeostasis and disregulation of iron balance caused by mutations in genes encoding proteins involved in iron transport, storage and metabolism. This review encompasses neurodegenerative disorders associated with both iron overload and deficiency to highlight areas where iron misregulation is likely to be important in the pathophysiology of several human brain diseases.

False

CitationGPTRetr11451

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Oxidative stress and redox-active iron in Alzheimer's disease. Abstract of the paper: Many lines of evidence indicate that oxidative stress is one of the earliest events in the genesis of Alzheimer's disease (AD). Iron is a transition metal capable of generating hydroxyl radicals, the most potent reactive oxygen species. Consequently, a disruption in the metabolism of iron has been postulated to have a role in the pathogenesis of AD. Indeed, both senile plaques and neurofibrillary tangles, the major pathological landmarks of AD, as well as neurons in the earliest stages of the disease, show elevated iron deposition. However, it is clear that the iron bound to lesion-associated proteins such as amyloid-beta and tau plays only a minor, late role in the disease, with the RNA-associated iron found in the neuronal cytoplasm occurring early and being of paramount importance. In this regard, it is probably not surprising that there is significant oxidation of cytoplasmic RNA among the populations of neurons vulnerable to AD. In this review, we consider the role of iron-induced oxidative stress as a key event in AD pathophysiology.

False

CitationGPTRetr11452

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Alzheimer Disease and Oxidative Stress. Abstract of the paper: Research in Alzheimer disease has recently demonstrated compelling evidence on the importance of oxidative processes in its pathogenesis. Cellular changes show that oxidative stress is an event that precedes the appearance of the hallmark pathologies of the disease, neurofibrillary tangles, and senile plaques. While it is still unclear what the initial source of the oxidative stress is in Alzheimer disease, it is likely that the process is highly dependent on redox-active transition metals such as iron and copper. Further investigation into the role that oxidative stress mechanisms seem to play in the pathogenesis of Alzheimer disease may lead to novel clinical interventions.

False

CitationGPTRetr11453

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Free radical damage, iron, and Alzheimer's disease. Abstract of the paper: We present evidence to support the premise that many of the pathological correlates of Alzheimer's disease are precipitated by free radical- and oxidative stress-induced mechanisms. We propose that amyloid-beta deposition in senile plaques, intracellular accumulation of protein in neurofibrillary tangles, and the degeneration of specific neuronal populations can be attributed to specific oxidative stress-type mechanisms. Free radicals in disease pathogenesis, generated in part as a result of Fenton-type reactions, suggest that lowering the level of available iron, intervention with antioxidants, or the administration of free radical scavengers could provide a therapeutic inroad in the fight against Alzheimer's disease.

False

CitationGPTRetr11454

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron on the brain. Abstract of the paper: Accumulations of iron are often detected in the brains of people suffering from neurodegenerative diseases. But it is often not known whether such accumulations contribute directly to disease progression. The identification of the genes mutated in two such disorders suggests that errors in iron metabolism do indeed have a key role.

False

CitationGPTRetr11455

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Abstract of the paper: Alzheimer's disease is the leading cause of dementia in the elderly and is defined by two pathological hallmarks; the accumulation of aggregated amyloid beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's disease progression is still debated, however, increased oxidative stress is an early and sustained event that underlies much of the neurotoxicity and consequent neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron promote amyloid beta oligomer formation. Additionally, copper and iron are redox active and can generate reactive oxygen species via Fenton (and Fenton-like chemistry) and the Haber-Weiss reaction. Copper, zinc and iron are naturally abundant in the brain but Alzheimer's disease brain contains elevated concentrations of these metals in areas of amyloid plaque pathology. Amyloid beta can become pro-oxidant and when complexed to copper or iron it can generate hydrogen peroxide. Accumulating evidence suggests that copper, zinc, and iron homeostasis may become perturbed in Alzheimer's disease and could underlie an increased oxidative stress burden. In this review we discuss oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that metals play in this process. Recent studies have started to elucidate molecular links with oxidative/nitrosative stress and Alzheimer's disease. Finally, we discuss metal binding compounds that are designed to cross the blood brain barrier and restore metal homeostasis as potential Alzheimer's disease therapeutics.

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CitationGPTRetr11456

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Unraveling the Burden of Iron in Neurodegeneration: Intersections with Amyloid Beta Peptide Pathology. Abstract of the paper: Iron overload is a hallmark of many neurodegenerative processes such as Alzheimer's, Parkinson's, and Huntington's diseases. Unbound iron accumulated as a consequence of brain aging is highly reactive with water and oxygen and produces reactive oxygen species (ROS) or free radicals. ROS are toxic compounds able to damage cell membranes, DNA, and mitochondria. Which are the mechanisms involved in neuronal iron homeostasis and in neuronal response to iron-induced oxidative stress constitutes a cutting-edge topic in metalloneurobiology. Increasing our knowledge about the underlying mechanisms that operate in iron accumulation and their consequences would shed light on the comprehension of the molecular events that participate in the pathophysiology of the abovementioned neurodegenerative diseases. In this review, current evidences about iron accumulation in the brain, the signaling mechanisms triggered by metal overload, as well as the interaction between amyloid β (Aβ) and iron, will be summarized.

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CitationGPTRetr11457

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron and Alzheimer's Disease: From Pathology to Imaging. Abstract of the paper: Alzheimer's disease (AD) is a debilitating brain disorder that afflicts millions worldwide with no effective treatment. Currently, AD progression has primarily been characterized by abnormal accumulations of β-amyloid within plaques and phosphorylated tau within neurofibrillary tangles, giving rise to neurodegeneration due to synaptic and neuronal loss. While β-amyloid and tau deposition are required for clinical diagnosis of AD, presence of such abnormalities does not tell the complete story, and the actual mechanisms behind neurodegeneration in AD progression are still not well understood. Support for abnormal iron accumulation playing a role in AD pathogenesis includes its presence in the early stages of the disease, its interactions with β-amyloid and tau, and the important role it plays in AD related inflammation. In this review, we present the existing evidence of pathological iron accumulation in the human AD brain, as well as discuss the imaging tools and peripheral measures available to characterize iron accumulation and dysregulation in AD, which may help in developing iron-based biomarkers or therapeutic targets for the disease.

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CitationGPTRetr11458

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Iron Pathophysiology in Alzheimer's Diseases. Abstract of the paper: Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. Increasing evidence suggests that disorders of metal ion metabolism in the brain are one of the risk factors for the pathogenesis of AD. Iron, one of the endogenous metal ions, involves in many important physiological activities in the brain. Iron metabolism mainly depends on iron regulatory proteins including ferritin, transferrin and transferrin receptor, hepcidin, ferroportin, lactoferrin. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, leads to cell death, and ultimately influences the process of β-amyloid (Aβ) misfolding and plaque aggregation. Although the results are different, in general, iron has deposition in different brain regions of AD patients, which may impair normal cognitive function and behavior. Therefore, neuroimaging changes have so far been largely attributed to focal iron deposition accompanying the plaques at preclinical stages of AD, and iron-targeted therapeutic strategies have become a new direction. Iron chelators have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Future research will also focus on iron as an opportunity to study the mechanism of the occurrence and development of AD from the iron steady state to more fully clarify the etiology and prevention strategies.

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CitationGPTRetr11459

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: excessive iron deposition may generate some of the oxidative stress know to occur in ad Title of the paper: Oxidative stress and neurodegeneration: the involvement of iron. Abstract of the paper: Many evidences indicate that oxidative stress plays a significant role in a variety of human disease states, including neurodegenerative diseases. Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing proteins and enzymes, though it could be also toxic. Actually, free iron excess generates oxidative stress, particularly in brain, where anti-oxidative defences are relatively low. Its accumulation in specific regions is associated with pathogenesis in a variety of neurodegenerative diseases (i.e., Parkinson's disease, Alzheimer's disease, Huntington's chorea, Amyotrophic Lateral Sclerosis and Neurodegeneration with Brain Iron Accumulation). Anyway, the extent of toxicity is dictated, in part, by the localization of the iron complex within the cell (cytosolic, lysosomal and mitochondrial), its biochemical form, i.e., ferritin or hemosiderin, as well as the ability of the cell to prevent the generation and propagation of free radical by the wide range of antioxidants and cytoprotective enzymes in the cell. Particularly, ferrous iron can act as a catalyst in the Fenton reaction that potentiates oxygen toxicity by generating a wide range of free radical species, including hydroxyl radicals (·OH). The observation that patients with neurodegenerative diseases show a dramatic increase in their brain iron content, correlated with the production of reactive oxigen species in these areas of the brain, conceivably suggests that disturbances in brain iron homeostasis may contribute to the pathogenesis of these disorders. The aim of this review is to describe the chemical features of iron in human beings and iron induced toxicity in neurodegenerative diseases. Furthermore, the attention is focused on metal chelating drugs therapeutic strategies.

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CitationGPTRetr11460

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: 2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents. Abstract of the paper: The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer cell growth and survival. Acting as a d-glucose mimic, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death. In addition to glycolysis inhibition, other molecular processes are also affected by 2-DG. Attempts to improve 2-DG's drug-like properties, its role as a potential adjuvant for other chemotherapeutics, and novel 2-DG analogs as promising new anticancer agents are discussed in this review.

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CitationGPTRetr11461

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Clinical studies for improving radiotherapy with 2-deoxy-D-glucose: present status and future prospects. Abstract of the paper: Higher rates of glucose usage generally correlate with poor prognosis in several types of malignant tumours. Experimental studies (both in vitro and in vivo) have shown that 2-deoxy-D-glucose (2-DG), a glucose analog and glycolytic inhibitor, enhances radiation-induced damage selectively in tumor cells while protecting normal cells, thereby suggesting that 2-DG can be used as a differential radiomodifier to improve the efficacy of radiotherapy. Clinical trials undertaken to study the feasibility, safety, and validity of this suggested approach will be described. Based on 2-DG-induced radiosensitization observed in primary organ cultures of cerebral glioma tissues, clinical trials were designed taking into consideration the radiobiology of gliomas and pharmacokinetics of 2-DG. Phase I/II clinical trials have unequivocally demonstrated that a combination of 2-DG (200-300 mg 2-DG per kg body weight orally administered after overnight fasting, 20 min before irradiation) with large weekly fractions (5 Gy/fraction) of low-LET radiotherapy is well tolerated without any acute toxicity or late radiation damage to the normal brain tissue. Nonserious transient side effects similar to hypoglycemia induced disturbances like restlessness, nausea, and vomiting were observed at the 2-DG doses used. Data from these trials involving more than 100 patients have clearly indicated a moderate increase in the survival, with a significant improvement in the quality of life with clinicopathological evidence of protection of normal brain tissue. A phase III multicentric trial to evaluate the efficacy of the combined treatment is in progress. Directions for future studies are discussed.

True

CitationGPTRetr11462

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth. Abstract of the paper: The glucose analogue 2-deoxy-D-glucose (2-DG) restrains growth of normal and malignant cells, prolongs the lifespan of C. elegans, and is widely used as a glycolytic inhibitor to study metabolic activity with regard to cancer, neurodegeneration, calorie restriction, and aging. Here, we report that separating glycolysis and the pentose phosphate pathway highly increases cellular tolerance to 2-DG. This finding indicates that 2-DG does not block cell growth solely by preventing glucose catabolism. In addition, 2-DG provoked similar concentration changes of sugar-phosphate intermediates in wild-type and 2-DG-resistant yeast strains and in human primary fibroblasts. Finally, a genome-wide analysis revealed 19 2-DG-resistant yeast knockouts of genes implicated in carbohydrate metabolism and mitochondrial homeostasis, as well as ribosome biogenesis, mRNA decay, transcriptional regulation, and cell cycle. Thus, processes beyond the metabolic block are essential for the biological properties of 2-DG.

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CitationGPTRetr11463

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Antiangiogenic activity of 2-deoxy-D-glucose. Abstract of the paper: BACKGROUND During tumor angiogenesis, endothelial cells (ECs) are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated. METHODOLOGY/PRINCIPAL FINDINGS In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO) N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR), which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay). Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETA)T(AG) transgenic retinoblastoma model. CONCLUSIONS/SIGNIFICANCE In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies.

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CitationGPTRetr11464

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Targeting tumor metabolism with 2-deoxyglucose in patients with castrate-resistant prostate cancer and advanced malignancies. Abstract of the paper: BACKGROUND A profound difference between cancer and normal tissues is the preferential utilization of glycolysis by cancer cells. To translate this paradigm in the clinic, we completed a phase I study of 2-deoxyglucose (2DG), and assessed 2DG uptake with fluorodeoxyglucose (FDG) positron emission tomography (PET) and the autophagy substrate p62 as a marker of 2DG resistance. METHODS Patients received 2DG orally on days 1-14 of a 21-day cycle in cohorts of three in a dose-escalating manner. Correlative assessments included PET scans at baseline and day 2 and p62 protein in peripheral blood mononuclear cells as a potential marker of 2DG resistance. RESULTS The dose of 45 mg/kg was defined as the recommended phase II dose, secondary to dose-limiting toxicity of grade 3 asymptomatic QTc prolongation at a dose of 60 mg/kg. PK evaluation of 2DG revealed linear pharmacokinetics with C(max) 45 microg/ml (277 microM), 73.7 microg/ml (449 microM), and 122 microg/ml (744 microM) in dose levels 30, 45, and 60 mg/kg, respectively. Five of eight patients assessed with FDG-PET scanning demonstrated decreased FDG uptake by day 2 of therapy, suggesting competition of 2DG with FDG. Five of six patients assessed for p62 had a decrease in p62 at 24 hr. CONCLUSIONS These data support the safety of 2DG, defined 2DG PK, demonstrated the effect of 2DG on FDG-PET imaging, and demonstrated the feasibility of assessment of p62 as an autophagic resistance marker. These data support future studies of 2DG alone or in combination with approaches to abrogate autophagy.

True

CitationGPTRetr11465

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: 2-deoxyribose deprives cultured astrocytes of their glutathione. Abstract of the paper: High concentrations of 2-deoxy-D-ribose (2dRib) have been reported to cause oxidative stress and to disturb the glutathione (GSH) metabolism of various cell types. Exposure of astrocyte-rich primary cultures to millimolar concentrations of 2dRib or its stereoisomer 2-deoxy-L-ribose, but not the incubation with ribose, 2-deoxyglucose, glucose, fructose or saccharose, lowered the cellular GSH content in a time and concentration dependent manner. After exposure for 4 h to 30 mM 2dRib the cells contained 2dRib in a concentration of about 24 mM. Under these conditions 2dRib did not compromise cell viability and the ability of the cells to synthesise GSH, nor were the cellular ratio of glutathione disulfide (GSSG) to GSH and the extracellular concentrations of GSH or GSSG increased. These data demonstrate that 2dRib deprives viable cultured astrocytes of GSH and suggest that a cellular reaction of GSH with 2dRib or its metabolites is involved in the deprivation of astrocytic GSH.

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CitationGPTRetr11466

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Principles of the 2-deoxyglucose method for the determination of the local cerebral glucose utilization. Abstract of the paper: Sokoloff and co-workers developed the 2-deoxy-D-[1-14C]glucose (2DG) method in order to study the local cerebral glucose utilization (LCGU) of discrete brain regions in vivo. Energy metabolism of the adult mammalian brain is almost entirely dependent on glucose. The majority of the glucose taken up by the brain is needed for the maintenance of the membrane potentials and the electrical activity. The functional activity could thus be shown to be closely linked to energy metabolism. Consequently, examination of the energy metabolism by measuring the cerebral metabolic rate for glucose can provide information concerning functional activity in all of the neuroanatomically defined regions of the brain. Studying the fate of experimentally injected 2-deoxy-D-[1-14C]glucose, a radioactive labeled analogue of glucose, and, subsequently, employing quantitative autoradiographic techniques, it is possible to estimate the levels of the local cerebral glucose utilization in specific regions of the brain. According to Sokoloff (1982) the LCGU represents a "metabolic encephalography".

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CitationGPTRetr11467

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Abstract of the paper: OBJECTIVE Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Because carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. METHODS Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K(+)](o), 4-aminopyridine, or bicuculline, and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring's mice, and maximal electroshock and subcutaneous pentylenetetrazol (Metrazol) in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. RESULTS 2DG (10mM) reduced interictal epileptiform bursts induced by 7.5mM [K(+)](o), 4-aminopyridine, and bicuculline, and electrographic seizures induced by high [K(+)](o) in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (effective dose [ED]50 = 79.7 mg/kg) and audiogenic stimulation in Fring's mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a twofold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. INTERPRETATION The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions, and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis.

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CitationGPTRetr11468

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Imaging brain deoxyglucose uptake and metabolism by glucoCEST MRI. Abstract of the paper: 2-Deoxy-D-glucose (2DG) is a known surrogate molecule that is useful for inferring glucose uptake and metabolism. Although (13)C-labeled 2DG can be detected by nuclear magnetic resonance (NMR), its low sensitivity for detection prohibits imaging to be performed. Using chemical exchange saturation transfer (CEST) as a signal-amplification mechanism, 2DG and the phosphorylated 2DG-6-phosphate (2DG6P) can be indirectly detected in (1)H magnetic resonance imaging (MRI). We showed that the CEST signal changed with 2DG concentration, and was reduced by suppressing cerebral metabolism with increased general anesthetic. The signal changes were not affected by cerebral or plasma pH, and were not correlated with altered cerebral blood flow as demonstrated by hypercapnia; neither were they related to the extracellular glucose amounts as compared with injection of D- and L-glucose. In vivo (31)P NMR revealed similar changes in 2DG6P concentration, suggesting that the CEST signal reflected the rate of glucose assimilation. This method provides a new way to use widely available MRI techniques to image deoxyglucose/glucose uptake and metabolism in vivo without the need for isotopic labeling of the molecules.

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CitationGPTRetr11469

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Use of nonradioactive 2-deoxyglucose to study compartmentation of brain glucose metabolism and rapid regional changes in rate. Abstract of the paper: A method is presented for measuring rapid changes in the rate of glucose phosphorylation in mouse brain with nonradioactive 2-deoxyglucose (DG). After times as short as 1 min after DG injection, the mouse is frozen rapidly, and selected brain regions are analyzed enzymatically for DG, 2-deoxyglucose 6-phosphate (DG6P), and glucose. The rate of glucose phosphorylation can be directly calculated from the rate of change in DG6P, the average levels of DG and glucose, and a constant derived from direct comparison of the rate of changes in glucose and DG6P after decapitation. Experiments with large brain samples provided evidence for a 2% per min loss of DG6P and at least two compartments differing in their rates of glucose metabolism, one rapidly entered by DG with glucose phosphorylation almost double that of average brain and another more slowly entered with a much lower phosphorylation rate. The method is illustrated by changes in phosphorylation within 2 min after injection of a convulsant or an anesthetic and over a 48-min time course with and without anesthesia. The sensitivity of the analytical methods can be amplified as much as desired by enzymatic cycling. Consequently, the method is applicable to very small brain samples. Examples are given for regions with volumes of 5 x 10(-4) microliters, but studies with samples as small as single large cell bodies are feasible.

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CitationGPTRetr11470

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Inhibition of established rat fibrosarcoma growth by the glucose antagonist 2-deoxy-D-glucose. Abstract of the paper: Sarcoma cells exhibit higher rates of glycolysis than normal tissues and may be dependent on glucose utilization for growth. Accordingly, we tested the ability of the glucose antimetabolite 2-deoxy-D-glucose (2-DG) to inhibit the growth of an established methylcholanthrene-induced rat fibrosarcoma in three groups of F344 rats with increasing subcutaneous inoculations of tumor (2 X 10(6) cells, 1 X 10(7) cells, and 1 mm tumor fragments). Rats were randomized to receive 2-DG or saline solution at doses of 0.75 gm/kg, 1.5 gm/kg, or 1.75 gm/kg, beginning 3 days after tumor implantation and continuing for 10 days. Tumors were removed and weighed on day 14. We measured tissue [14C]-2-DG levels in tumor, brain, liver, and muscle after intraperitoneal injection of radiolabeled 2-DG. In these same tissues we determined the activity of glucose-6-phosphatase (G-6-Pase), an enzyme which dephosphorylates the intracellular glycolytic inhibitor 2-DG-6-phosphate, thus reversing the antitumor effect of 2-DG. All groups treated with 2-DG had a significant reduction in tumor weight of 50% to 70% when compared with saline solution-treated controls. Toxicity was substantial at the highest dose of 2-DG, but minimal toxicity was noted at intermediate and low doses. Tumor had the greatest uptake of [14C]-2-DG, with low levels of G-6-Pase leading to prolonged retention and highest tissue levels of radiolabeled 2-DG. Use of 2-DG inhibits established sarcoma growth because it is rapidly transported into tumors, cannot be metabolized after phosphorylation, and is dephosphorylated and released slowly from tumor cells. Rat sarcoma growth is dependent on glucose utilization and can be effectively inhibited by glucose antagonism.

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CitationGPTRetr11471

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats. Abstract of the paper: Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

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CitationGPTRetr11472

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: 2-Deoxyglucose and Beta-Hydroxybutyrate: Metabolic Agents for Seizure Control. Abstract of the paper: Current anti-seizure drugs (ASDs) are believed to reduce neuronal excitability through modulation of ion channels and transporters that regulate excitability at the synaptic level. While most patients with epilepsy respond to ASDs, many remain refractory to medical treatment but respond favorably to a high-fat, low-carbohydrate metabolism-based therapy known as the ketogenic diet (KD). The clinical effectiveness of the KD has increasingly underscored the thesis that metabolic factors also play a crucial role in the dampening neuronal hyperexcitability that is a hallmark feature of epilepsy. This notion is further amplified by the clinical utility of other related metabolism-based diets such as the modified Atkins diet and the low-glycemic index treatment (LGIT). Traditional high-fat diets are characterized by enhanced fatty acid oxidation (which produces ketone bodies such as beta-hydroxybutyrate) and a reduction in glycolytic flux, whereas the LGIT is predicated mainly on the latter observation of reduced blood glucose levels. As dietary implementation is not without challenges regarding clinical administration and patient compliance, there is an inherent desire and need to determine whether specific metabolic substrates and/or enzymes might afford similar clinical benefits, hence validating the concept of a "diet in a pill." Here, we discuss the evidence for one glycolytic inhibitor, 2-deoxyglucose (2DG) and one metabolic substrate, β-hydroxybutyrate (BHB) exerting direct effects on neuronal excitability, highlight their mechanistic differences, and provide the strengthening scientific rationale for their individual or possibly combined use in the clinical arena of seizure management.

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CitationGPTRetr11473

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: 2-deoxy-d-ribose induces apoptosis by inhibiting the synthesis and increasing the efflux of glutathione. Abstract of the paper: Oxidative stress is caused by imbalance between the production of reactive oxygen species (ROS) and biological system ability to readily detoxify the reactive intermediates or repair the resulting damage. 2-deoxy-D-ribose (dRib) is known to induce apoptosis by provoking an oxidative stress by depleting glutathione (GSH). In this paper, we elucidate the mechanisms underlying GSH depletion in response to dRib treatment. We demonstrated that the observed GSH depletion is not only due to inhibition of synthesis, by inhibiting gamma-glutamyl-cysteine synthetase, but also due to its increased efflux, by the activity of multidrug resistance associated proteins transporters. We conclude that dRib interferes with GSH homeostasis and that likely cellular oxidative stress is a consequence of GSH depletion. Various GSH fates, such as direct oxidation, lack of synthesis or of storage, characterize different kinds of oxidative stress. In the light of our observations we conclude that dRib does not induce GSH oxidation but interferes with GSH synthesis and storage. Lack of GSH allows accumulation of ROS and cells, disarmed against oxidative insults, undergo apoptosis.

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CitationGPTRetr11474

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: The highly reducing sugar 2-deoxy-D-ribose induces apoptosis in human fibroblasts by reduced glutathione depletion and cytoskeletal disruption. Abstract of the paper: 2-deoxy-D-Ribose (dRib), the most reducing sugar, induces apoptosis in normal human fibroblasts, as judged by cytoplasmic shrinkage, chromatin condensation, DNA fragmentation and mitochondrial depolarization. This effect is independent from culture conditions, such as cell density and the presence or absence of serum in the culture milieu, suggesting that dRib-induced apoptosis is cell cycle-independent. dRib was found also to provoke disruption of the actin filament network and detachment from the substratum, while at the same time, interestingly, it increases the expression of several integrins and cell adhesion molecules. Furthermore, dRib was found to reduce the intracellular levels of reduced glutathione (GSH). The apoptotic process was not affected by the macromolecular-synthesis inhibitors cycloheximide and actinomycin D. On the contrary, the antioxidant N-acetyl-L-cysteine (NAC) fully blocks the dRib-induced apoptosis by preventing GSH depletion, while it also inhibits actin-filament-network disruption and mitochondrial depolarization. The above indicate that dRib induces apoptosis in human fibroblasts by a mechanism involving glutathione metabolism and oxidative stress, as well as disturbance of cytoskeletal integrity and cell adhesion.

False

CitationGPTRetr11475

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: PET imaging of glucose metabolism in a mouse model of temporal lobe epilepsy. Abstract of the paper: Here we present the first demonstration that 2-deoxy-2[18F]fluoro-D-glucose (18FDG) and micro Positron Emission Tomography (microPET) can be used successfully to monitor regional changes in brain metabolism during acute seizure induction in C57Bl/6 mice. These longitudinal studies show a significant increase in 18FDG uptake in the hippocampus (33.2%) which correlates directly with seizure severity (R2=0.86). 18FDG microPET can potentially be used to monitor the development of TLE in mouse models from the acute phase of status epilepticus to the chronic phase of spontaneous recurrent seizures. These studies provide a foundation upon which we can begin to identify genetic contributions to the metabolic signature of TLE in mice, since many transgenics are in the C57Bl/6 background strain.

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CitationGPTRetr11476

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) induces cell death through caspase-independent mechanism in A172 human glioma cells. Abstract of the paper: 15-Deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ(2)) is a naturally occurring cyclopentenone metabolite of prostaglandin D(2) (PGD(2)) and is known as a specific potent ligand for the peroxisome proliferators activator receptor-gamma (PPARgamma). 15d-PGJ(2) inhibits cell growth and induces apoptosis in a number of different cancer cells. However, the underlying mechanism by which 15d-PGJ(2) induces cell death remains to be defined. The present study was undertaken to determine the effect of 15d-PGJ(2) on cell death in A172 human glioma cells. 15d-PGJ(2) caused reactive oxygen species (ROS) generation. 15d-PGJ(2)-induced ROS production and cell death were prevented by the antioxidant N-acetylcysteine. Activation of mitogen-activated protein kinases (MAPK) was not observed in cells treated with 15d-PGJ(2 )and inhibitors of MAPK subfamilies also were not effective in preventing 15d-PGJ(2)-induced cell death. 15d-PGJ(2) treatment caused mitochondrial dysfunction, as evidenced by depolarization of mitochondrial membrane potential. 15d-PGJ(2) induced caspase activation at 24 h of treatment, but the 15d-PGJ(2)-induced cell death was not prevented by caspase inhibitors. The antiapoptotic protein XIAP levels and release of apoptosis inducing factor (AIF) into the cytosol were not altered by 15d-PGJ(2) treatment. Taken together, these findings indicate that 15d-PGJ(2) triggers cell death through a caspase-independent mechanism and ROS production and disruption of mitochondrial membrane potential play an important role in the 15d-PGJ(2)-induced cell death in A172 human glioma cells.

False

CitationGPTRetr11477

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: In vivo 2-deoxyglucose administration preserves glucose and glutamate transport and mitochondrial function in cortical synaptic terminals after exposure to amyloid beta-peptide and iron: evidence for a stress response. Abstract of the paper: Mild metabolic stress can increase resistance of neurons in the brain to subsequent more severe insults, as exemplified by the beneficial effects of heat shock and ischemic preconditioning. Studies of Alzheimer's disease and other age-related neurodegenerative disorders indicate that dysfunction and degeneration of synapses occur early in the cell death process, and that oxidative stress and mitochondrial dysfunction are central events in this pathological process. It was recently shown that administration of 2-deoxy-d-glucose (2DG), a nonmetabolizable glucose analog that induces metabolic stress, to rats and mice can increase resistance of neurons in the brain to excitotoxic, ischemic, and oxidative injury. We now report that administration of 2DG to adult rats (daily i.p. injections of 100 mg/kg body weight) increases resistance of synaptic terminals to dysfunction and degeneration induced by amyloid beta-peptide and ferrous iron, an oxidative insult. The magnitude of impairment of glucose and glutamate transport induced by amyloid beta-peptide and iron was significantly reduced in cortical synaptosomes from 2DG-treated rats compared to saline-treated control rats. Mitochondrial dysfunction, as indicated by increased levels of reactive oxygen species and decreased transmembrane potential, was significantly attenuated after exposure to amyloid beta-peptide and iron in synaptosomes from 2DG-treated rats. Levels of the stress proteins HSP-70 and GRP-78 were increased in synaptosomes from 2DG-treated rats, suggesting a mechanism whereby 2DG protects synaptic terminals. We conclude that 2DG bolsters cytoprotective mechanisms within synaptic terminals, suggesting novel preventative and therapeutic approaches for neurodegenerative disorders.

False

CitationGPTRetr11478

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination. Abstract of the paper: The 2-deoxyglucose (2-DG) method of functional neuroanatomical mapping25 was re-examined in order to (1) obtain physical descriptions of the transfer constants K1 and k2, (2) estimate the changes of the 'lumped constant' with the condition of the experimental animals, and (3) examine the use of 3-O-methylglucose (3-O-MG) to estimate the fraction of unphosphorylated 2-DG in the tissue, and the value of the 'lumped constant'. The transfer constants K1 and k2 were shown to be simple exponential forms of the apparent permeability of the cerebral capillary endothelium to glucose and glucose analogs. The 'lumped constant' was shown to be influenced by any reduction of the ratio between glucose transport and glucose phosphorylation in the tissue, e.g. by hypoglycemia and increased glycolysis, while hyperglycemia and decreased glycolysis resulted in very minor changes of the 'lumped constant'. The glucose analog 3-O-MG was shown accurately to trace unphosphorylated 2-DG in brain and to be an index of the brain content of glucose and the regional value of the 'lumped constant'. In addition, 3-O-MG proved to be an accurate tracer of unphosphorylated 2-DG for experimental times as low as 10 min.

False

CitationGPTRetr11479

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the safety profile of 2dg has been investigated in multiple preclinical and clinical studies Title of the paper: Decreased brain glucose metabolism in microvessels from patients with Alzheimer's disease. Abstract of the paper: We studied brain glucose metabolism in patients with Alzheimer's disease and age-matched controls in vivo by PET and assessed brain glucose utilization and the phosphorylation constant K3 for hexokinase. In addition we determined in vitro the binding of 2DG and measured its phosphorylation to 2DG-phosphate in cerebral microvessels obtained at autopsy from subjects with Alzheimer's disease and age-matched controls. In patients with Alzheimer's disease we found a marked decrease in the kinetic constant K3 for the hexokinase, and a marked decrease in the overall metabolism of glucose in our PET studies; in microvessels there was a marked decrease in the affinity of 2DG and a decrease in hexokinase activity. Alzheimer's disease may be related to a complex alteration in brain glucose metabolism.

False

CitationGPTRetr11480

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Amyloid beta deregulates astroglial mGluR5-mediated calcium signaling via calcineurin and Nf-kB. Abstract of the paper: The amyloid hypothesis of Alzheimer's disease (AD) suggests that soluble amyloid β (Aβ) is an initiator of a cascade of events eventually leading to neurodegeneration. Recently, we reported that Aβ deranged Ca(2+) homeostasis specifically in hippocampal astrocytes by targeting key elements of Ca(2+) signaling, such as mGluR5 and IP3 R1. In the present study, we dissect a cascade of signaling events by which Aβ deregulates glial Ca(2+) : (i) 100 nM Aβ leads to an increase in cytosolic calcium after 4-6 h of treatment; (ii) mGluR5 is increased after 24 h of treatment; (iii) this increase is blocked by inhibitors of calcineurin (CaN) and NF-kB. Furthermore, we show that Aβ treatment of glial cells leads to de-phosphorylation of Bcl10 and an increased CaN-Bcl10 interaction. Last, mGluR5 staining is augmented in hippocampal astrocytes of AD patients in proximity of Aβ plaques and co-localizes with nuclear accumulation of the p65 NF-kB subunit and increased staining of CaNAα. Taken together our data suggest that nanomolar [Aβ] deregulates Ca(2+) homeostasis via CaN and its downstream target NF-kB, possibly via the cross-talk of Bcl10 in hippocampal astrocytes.

False

CitationGPTRetr11481

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Amyloid beta peptide 1-42 disturbs intracellular calcium homeostasis through activation of GluN2B-containing N-methyl-d-aspartate receptors in cortical cultures. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to debilitating cognitive deficits. Recent evidence demonstrates that glutamate receptors are dysregulated by amyloid beta peptide (Aβ) oligomers, resulting in disruption of glutamatergic synaptic transmission which parallels early cognitive deficits. Although it is well accepted that neuronal death in AD is related to disturbed intracellular Ca(2+) (Ca(2+)(i)) homeostasis, little is known about the contribution of NMDARs containing GluN2A or GluN2B subunits on Aβ-induced Ca(2+)(i) rise and neuronal dysfunction. Thus, the main goal of this work was to evaluate the role of NMDAR subunits in dysregulation of Ca(2+)(i) homeostasis induced by Aβ 1-42 preparation containing both oligomers (in higher percentage) and monomers in rat cerebral cortical neurons. The involvement of NMDARs was evaluated by pharmacological inhibition with MK-801 or the selective GluN2A and GLUN2B subunit antagonists NVP-AAM077 and ifenprodil, respectively. We show that Aβ, like NMDA, increase Ca(2+)(i) levels mainly through activation of NMDARs containing GluN2B subunits. Conversely, GluN2A-NMDARs antagonism potentiates Ca(2+)(i) rise induced by a high concentration of Aβ (1μM), suggesting that GluN2A and GluN2B subunits have opposite roles in regulating Ca(2+)(i) homeostasis. Moreover, Aβ modulate NMDA-induced responses and vice versa. Indeed, pre-exposure to Aβ (1μM) decrease NMDA-evoked Ca(2+)(I) rise and pre-exposure to NMDA decrease Aβ response. Interestingly, simultaneous addition of Aβ and NMDA potentiate Ca(2+)(I) levels, this effect being regulated by GluN2A and GluN2B subunits in opposite manners. This study contributes to the understanding of the molecular basis of early AD pathogenesis, by exploring the role of GluN2A and GluN2B subunits in the mechanism of Aβ toxicity in AD.

False

CitationGPTRetr11482

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Dysregulation of calcium homeostasis in Alzheimer's disease. Abstract of the paper: The accumulation of oligomeric species of beta-amyloid protein in the brain is considered to be a key factor that causes Alzheimer's disease (AD). However, despite many years of research, the mechanism of neurotoxicity in AD remains obscure. Recent evidence strongly supports the theory that Ca2+ dysregulation is involved in AD. Amyloid proteins have been found to induce Ca2+ influx into neurons, and studies on transgenic mice suggest that this Ca2+ influx may alter neuronal excitability. The identification of a risk factor gene for AD that may be involved in the regulation of Ca2+ homeostasis and recent findings which suggest that presenilins may be involved in the regulation of intracellular Ca2+ stores provide converging lines of evidence that support the idea that Ca2+ dysregulation is a key step in the pathogenesis of AD.

False

CitationGPTRetr11483

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Neuronal and glial calcium signaling in Alzheimer's disease. Abstract of the paper: Cognitive impairment and emotional disturbances in Alzheimer's disease (AD) result from the degeneration of synapses and death of neurons in the limbic system and associated regions of the cerebral cortex. An alteration in the proteolytic processing of the amyloid precursor protein (APP) results in increased production and accumulation of amyloid beta-peptide (Abeta) in the brain. Abeta has been shown to cause synaptic dysfunction and can render neurons vulnerable to excitotoxicity and apoptosis by a mechanism involving disruption of cellular calcium homeostasis. By inducing membrane lipid peroxidation and generation of the aldehyde 4-hydroxynonenal, Abeta impairs the function of membrane ion-motive ATPases and glucose and glutamate transporters, and can enhance calcium influx through voltage-dependent and ligand-gated calcium channels. Reduced levels of a secreted form of APP which normally regulates synaptic plasticity and cell survival may also promote disruption of synaptic calcium homeostasis in AD. Some cases of inherited AD are caused by mutations in presenilins 1 and 2 which perturb endoplasmic reticulum (ER) calcium homeostasis such that greater amounts of calcium are released upon stimulation, possibly as the result of alterations in IP(3) and ryanodine receptor channels, Ca(2+)-ATPases and the ER stress protein Herp. Abnormalities in calcium regulation in astrocytes, oligodendrocytes, and microglia have also been documented in studies of experimental models of AD, suggesting contributions of these alterations to neuronal dysfunction and cell death in AD. Collectively, the available data show that perturbed cellular calcium homeostasis plays a prominent role in the pathogenesis of AD, suggesting potential benefits of preventative and therapeutic strategies that stabilize cellular calcium homeostasis.

False

CitationGPTRetr11484

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Alzheimer's disease-associated peptide Aβ42 mobilizes ER Ca(2+) via InsP3R-dependent and -independent mechanisms. Abstract of the paper: Dysregulation of Ca(2+) homeostasis is considered to contribute to the toxic action of the Alzheimer's disease (AD)-associated amyloid-β-peptide (Aβ). Ca(2+) fluxes across the plasma membrane and release from intracellular stores have both been reported to underlie the Ca(2+) fluxes induced by Aβ42. Here, we investigated the contribution of Ca(2+) release from the endoplasmic reticulum (ER) to the effects of Aβ42 upon Ca(2+) homeostasis and the mechanism by which Aβ42 elicited these effects. Consistent with previous reports, application of soluble oligomeric forms of Aβ42 induced an elevation in intracellular Ca(2+). The Aβ42-stimulated Ca(2+) signals persisted in the absence of extracellular Ca(2+) indicating a significant contribution of Ca(2+) release from the ER Ca(2+) store to the generation of these signals. Moreover, inositol 1,4,5-trisphosphate (InsP3) signaling contributed to Aβ42-stimulated Ca(2+) release. The Ca(2+) mobilizing effect of Aβ42 was also observed when applied to permeabilized cells deficient in InsP3 receptors, revealing an additional direct effect of Aβ42 upon the ER, and a mechanism for induction of toxicity by intracellular Aβ42.

False

CitationGPTRetr11485

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Abstract of the paper: Perturbed neuronal Ca(2+) homeostasis is implicated in age-related cognitive impairment and Alzheimer's disease (AD). With advancing age, neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular Ca(2+) dynamics. Toxic forms of amyloid beta-peptide (Abeta) can induce Ca(2+) influx into neurons by inducing membrane-associated oxidative stress or by forming an oligomeric pore in the membrane, thereby rendering neurons vulnerable to excitotoxicity and apoptosis. AD-causing mutations in the beta-amyloid precursor protein and presenilins can compromise these normal proteins in the plasma membrane and endoplasmic reticulum, respectively. Emerging knowledge of the actions of Ca(2+) upstream and downstream of Abeta provides opportunities to develop novel preventative and therapeutic interventions for AD.

False

CitationGPTRetr11486

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Calcium Dyshomeostasis in Alzheimer's Disease Pathogenesis. Abstract of the paper: Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder that is characterized by amyloid β-protein deposition in senile plaques, neurofibrillary tangles consisting of abnormally phosphorylated tau protein, and neuronal loss leading to cognitive decline and dementia. Despite extensive research, the exact mechanisms underlying AD remain unknown and effective treatment is not available. Many hypotheses have been proposed to explain AD pathophysiology; however, there is general consensus that the abnormal aggregation of the amyloid β peptide (Aβ) is the initial event triggering a pathogenic cascade of degenerating events in cholinergic neurons. The dysregulation of calcium homeostasis has been studied considerably to clarify the mechanisms of neurodegeneration induced by Aβ. Intracellular calcium acts as a second messenger and plays a key role in the regulation of neuronal functions, such as neural growth and differentiation, action potential, and synaptic plasticity. The calcium hypothesis of AD posits that activation of the amyloidogenic pathway affects neuronal Ca2+ homeostasis and the mechanisms responsible for learning and memory. Aβ can disrupt Ca2+ signaling through several mechanisms, by increasing the influx of Ca2+ from the extracellular space and by activating its release from intracellular stores. Here, we review the different molecular mechanisms and receptors involved in calcium dysregulation in AD and possible therapeutic strategies for improving the treatment.

False

CitationGPTRetr11487

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Network-wide dysregulation of calcium homeostasis in Alzheimer's disease. Abstract of the paper: Dysregulation of intracellular Ca(2+) homeostasis has been proposed as a common proximal cause of neural dysfunction during aging and Alzheimer's disease (AD). In this context, aberrant Ca(2+) signaling has been viewed as a neuronal phenomenon mostly related to the dysfunction of intracellular Ca(2+) stores. However, recent data suggest that, in AD, Ca(2+) dyshomeostasis is not restricted to neurons but represents a global phenomenon affecting virtually all cells in the brain. AD-related aberrant Ca(2+) signaling in astrocytes and microglia, which is activated during the disease, probably contributes profoundly to an inflammatory response that, in turn, impacts neuronal Ca(2+) homeostasis and brain function. Based on recent data obtained in vivo and in vitro, we propose that bidirectional interactions between the inflammatory responses of glial cells and aberrant Ca(2+) signaling represent a vicious cycle accelerating disease progression.

False

CitationGPTRetr11488

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Ca2+ influx through store-operated Ca2+ channels reduces Alzheimer disease β-amyloid peptide secretion. Abstract of the paper: Alzheimer disease (AD), the leading cause of dementia, is characterized by the accumulation of β-amyloid peptides (Aβ) in senile plaques in the brains of affected patients. Many cellular mechanisms are thought to play important roles in the development and progression of AD. Several lines of evidence point to the dysregulation of Ca(2+) homeostasis as underlying aspects of AD pathogenesis. Moreover, direct roles in the regulation of Ca(2+) homeostasis have been demonstrated for proteins encoded by familial AD-linked genes such as PSEN1, PSEN2, and APP, as well as Aβ peptides. Whereas these studies support the hypothesis that disruption of Ca(2+) homeostasis contributes to AD, it is difficult to disentangle the effects of familial AD-linked genes on Aβ production from their effects on Ca(2+) homeostasis. Here, we developed a system in which cellular Ca(2+) homeostasis could be directly manipulated to study the effects on amyloid precursor protein metabolism and Aβ production. We overexpressed stromal interaction molecule 1 (STIM1) and Orai1, the components of the store-operated Ca(2+) entry pathway, to generate cells with constitutive and store depletion-induced Ca(2+) entry. We found striking effects of Ca(2+) entry induced by overexpression of the constitutively active STIM1(D76A) mutant on amyloid precursor protein metabolism. Specifically, constitutive activation of Ca(2+) entry by expression of STIM1(D76A) significantly reduced Aβ secretion. Our results suggest that disruptions in Ca(2+) homeostasis may influence AD pathogenesis directly through the modulation of Aβ production.

False

CitationGPTRetr11489

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Calcium-regulated signaling pathways: role in amyloid beta-induced synaptic dysfunction. Abstract of the paper: Amyloid beta (Abeta) peptides have been shown to impair synaptic function, especially long-term synaptic plasticity, in transgenic mouse models of Alzheimer's disease (AD) and in acute hippocampal preparations. In the transgenic mice overexpressing mutant forms of human amyloid precursor protein (APP), the deficits in hippocampal long-term potentiation (LTP) occur prior to synaptic loss and cell death, suggesting early functional changes at these synapses. Recent studies demonstrate that Abeta-induced synaptic dysfunction is linked with altered Ca2+ signaling in hippocampal neurons. While reducing Ca2+ influx through NMDA receptors, Abeta peptides elevate intracellular Ca2+ concentration by enhancing Ca2+ influx from voltage-gated Ca2+ channels or nonselective cation channels, or by stimulating Ca2+ release from intracellular stores. Interestingly, acute application of Abeta or APP overexpression inhibits activity-dependent regulation of several protein kinase pathways that require Ca2+ influx via NMDA receptors for activation, including Ca2+/calmodulin-dependent protein kinase II, protein kinase A, and extracellular regulated kinases (Erk). On the other hand, activation of Ca2+-dependent protein phosphatase 2B (calcineurin) is implicated in Abeta inhibition of LTP. Thus, multiple Ca2+-regulated signaling pathways are involved in the synaptic action of Abeta, and malfunction of these pathways may underlie the synaptic dysfunction in early AD.

False

CitationGPTRetr11490

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Functional interplay between plasma membrane Ca2+-ATPase, amyloid β-peptide and tau. Abstract of the paper: It is well known that dysregulation of Ca2+ homeostasis is involved in Alzheimeŕs disease (AD), a neurodegenerative disorder characterized by the presence of toxic aggregates of amyloid β-peptide (Aβ) and neurofibrillary tangles of tau. Alteration of calcium signaling has been linked to Aβ and tau pathologies, although the understanding of underlying molecular and cellular mechanisms is far from clear. This review summarizes the functional inhibition of plasma membrane Ca2+-ATPase (PMCA) by Aβ and tau, and its modulation by calmodulin and the ionic nature of phospholipids. The data obtained until now in our laboratory suggest that PMCA injury linked to Aβ and tau can be significantly involved in the cascade of events leading to intracellular calcium overload associated to AD.

False

CitationGPTRetr11491

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Calcium dysregulation in Alzheimer's disease. Abstract of the paper: Alzheimer disease (AD) is the most common form of adult dementia. Its pathological hallmarks are synaptic degeneration, deposition of amyloid plaques and neurofibrillary tangles, leading to neuronal loss. A few hypotheses have been proposed to explain AD pathogenesis. The beta-amyloid (Abeta) and hyperphosphorylated tau hypotheses suggest that these proteins are the main players in AD development. Another hypothesis proposes that the dysregulation of calcium homeostasis may be a key factor in accelerating other pathological changes. Although Abeta and tau have been extensively studied, recently published data provide a growing body of evidence supporting the critical role of calcium signalling in AD. For example, presenilins, which are mutated in familial cases of AD, were demonstrated to form low conductance calcium channels in the ER and elevated cytosolic calcium concentration increases amyloid generation. Moreover, memantine, an antagonist of the NMDA-calcium channel receptor, has been found to have a beneficial effect for AD patients offering novel possibilities for a calcium signalling targeted therapy of AD. This review underscores the growing importance of calcium ions in AD development and focuses on the relevant aspects of calcium homeostasis.

False

CitationGPTRetr11492

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer's Disease. Abstract of the paper: Ca2+ homeostasis is essential for multiple neuronal functions and thus, Ca2+ dyshomeostasis can lead to widespread impairment of cellular and synaptic signaling, subsequently contributing to dementia and Alzheimer's disease (AD). While numerous studies implicate Ca2+ mishandling in AD, the cellular basis for loss of cognitive function remains under investigation. The process of synaptic degradation and degeneration in AD is slow, and constitutes a series of maladaptive processes each contributing to a further destabilization of the Ca2+ homeostatic machinery. Ca2+ homeostasis involves precise maintenance of cytosolic Ca2+ levels, despite extracellular influx via multiple synaptic Ca2+ channels, and intracellular release via organelles such as the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) and IP3R, lysosomes via transient receptor potential mucolipin channel (TRPML) and two pore channel (TPC), and mitochondria via the permeability transition pore (PTP). Furthermore, functioning of these organelles relies upon regulated inter-organelle Ca2+ handling, with aberrant signaling resulting in synaptic dysfunction, protein mishandling, oxidative stress and defective bioenergetics, among other consequences consistent with AD. With few effective treatments currently available to mitigate AD, the past few years have seen a significant increase in the study of synaptic and cellular mechanisms as drivers of AD, including Ca2+ dyshomeostasis. Here, we detail some key findings and discuss implications for future AD treatments.

False

CitationGPTRetr11493

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Calcium signaling and amyloid toxicity in Alzheimer disease. Abstract of the paper: Intracellular Ca(2+) signaling is fundamental to neuronal physiology and viability. Because of its ubiquitous roles, disruptions in Ca(2+) homeostasis are implicated in diverse disease processes and have become a major focus of study in multifactorial neurodegenerative diseases such as Alzheimer disease (AD). A hallmark of AD is the excessive production of beta-amyloid (Abeta) and its massive accumulation in amyloid plaques. In this minireview, we highlight the pathogenic interactions between altered cellular Ca(2+) signaling and Abeta in its different aggregation states and how these elements coalesce to alter the course of the neurodegenerative disease. Ca(2+) and Abeta intersect at several functional levels and temporal stages of AD, thereby altering neurotransmitter receptor properties, disrupting membrane integrity, and initiating apoptotic signaling cascades. Notably, there are reciprocal interactions between Ca(2+) pathways and amyloid pathology; altered Ca(2+) signaling accelerates Abeta formation, whereas Abeta peptides, particularly in soluble oligomeric forms, induce Ca(2+) disruptions. A degenerative feed-forward cycle of toxic Abeta generation and Ca(2+) perturbations results, which in turn can spin off to accelerate more global neuropathological cascades, ultimately leading to synaptic breakdown, cell death, and devastating memory loss. Although no cause or cure is currently known, targeting Ca(2+) dyshomeostasis as an underlying and integral component of AD pathology may result in novel and effective treatments for AD.

False

CitationGPTRetr11494

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Role of calcium in the pathogenesis of Alzheimer's disease and transgenic models. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly that is characterized by memory loss. Neuropathologically, the AD brain is marked by an increased AP burden, hyperphosphorylated tau aggregates, synaptic loss, and inflammatory responses. Disturbances in calcium homeostasis are also one of the earliest molecular changes that occur in AD patients, alongside alterations in calcium-dependent enzymes in the post-mortem brain. The sum of these studies suggests that calcium dyshomeostasis is an integral part of the pathology, either influencing AP production, mediating its effects or both. Increasing evidence from in vitro studies demonstrates that the AP peptide could modulate a number of ion channels increasing calcium influx, including voltage-gated calcium and potassium channels, the NMDA receptor, the nicotinic receptor, as well as forming its own calcium-conducting pores. In vivo evidence has shown that A3 impairs both LTP and cognition, whereas all of these ion channels cluster at the synapse and underlie synaptic transmission and hence cognition. Here we consider the evidence that AP causes cognitive deficits through altering calcium homeostasis at the synapse, thus impairing synaptic transmission and LTP. Furthermore, this disruption appearr to occur without overt or extensive neuronal loss, as it is observed in transgenic mouse models of AD, but may contribute to the synaptic loss, which is an early event that correlates best with cognitive decline.

False

CitationGPTRetr11495

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Beta-amyloid causes downregulation of calcineurin in neurons through induction of oxidative stress. Abstract of the paper: Calcineurin is an abundant cytosolic protein that is implicated in the modulation of glutamate release. Here we show that the expression level of this enzyme is reduced in primary neuronal cultures treated with beta-amyloid. Parallel experiments in ETNA cell lines expressing SOD1 suggested that the effect of beta-amyloid on calcineurin expression is mediated by oxidative stress. The relevance of the in vitro experiments was assessed by analysis of tissue from patients with Alzheimer's disease (AD) and tissue from two strains of transgenic mice that mimic aspects of AD. The tissue from the AD brains displayed a pronounced downregulation of calcineurin immunoreactivity in profiles that were negative for glial fibrillary acidic protein (GFAP). In the hippocampus of the transgenic animals (which were analyzed in an early stage of the disease) the downregulation of calcineurin was restricted to mossy fiber terminals. A downregulation of the presynaptic pool of calcineurin may contribute to the dysregulation of glutamate release that is considered a hallmark of AD.

False

CitationGPTRetr11496

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits. Abstract of the paper: Calcium is one of the most important intracellular messengers in the brain, being essential for neuronal development, synaptic transmission and plasticity, and the regulation of various metabolic pathways. The findings reviewed in the present article suggest that calcium also plays a prominent role in the pathogenesis of Alzheimer's disease (AD). Associations between the pathological hallmarks ofAD (neurofibrillary tangles [NFT] and amyloid plaques) and perturbed cellular calcium homeostasis have been established in studies of patients, and in animal and cell culture models of AD. Studies of the effects of mutations in the beta-amyloid precursor protein (APP) and presenilins on neuronal plasticity and survival have provided insight into the molecular cascades that result in synaptic dysfunction and neuronal degeneration in AD. Central to the neurodegenerative process is the inability of neurons to properly regulate intracellular calcium levels. Increased levels of amyloid beta-peptide (Abeta) induce oxidative stress, which impairs cellular ion homeostasis and energy metabolism and renders neurons vulnerable to apoptosis and excitotoxicity. Subtoxic levels of Abeta may induce synaptic dysfunction by impairing multiple signal transduction pathways. Presenilin mutations perturb calcium homeostasis in the endoplasmic reticulum in a way that sensitizes neurons to apoptosis and excitotoxicity; links between aberrant calcium regulation and altered APP processing are emerging. Environmental risk factors for AD are being identified and may include high calorie diets, folic acid insufficiency, and a low level of intellectual activity (bad habits); in each case, the environmental factor impacts on neuronal calcium homeostasis. Low calorie diets and intellectual activity may guard against AD by stimulating production of neurotrophic factors and chaperone proteins. The emerging picture of the cell and molecular biology of AD is revealing novel preventative and therapeutic strategies for eradicating this growing epidemic of the elderly.

False

CitationGPTRetr11497

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease. Abstract of the paper: Recent findings link altered processing of beta-amyloid precursor protein (beta APP) to disruption of neuronal Ca2+ homeostasis and an excitotoxic mechanism of cell death in Alzheimer's disease. A major pathway of beta APP metabolism results in the release of secreted forms of beta APP, APPss. These secreted forms are released in response to electrical activity and can modulate neuronal responses to glutamate, suggesting roles in developmental and synaptic plasticity. beta APP is upregulated in response to neural injury and APPss can protect neurons against excitotoxic or ischemic insults by stabilizing the intracellular Ca2+ concentration [Ca2+]i. An alternative beta APP processing pathway liberates intact beta-amyloid peptide, which can form aggregates that disrupt Ca2+ homeostasis and render neurons vulnerable to metabolic or excitotoxic insults. Genetic abnormalities (e.g. certain beta APP mutations or Down syndrome) and age-related changes in brain metabolism (e.g. reduced energy availability or increased oxidative stress) may favor accumulation of [Ca2+]i-destabilizing beta-amyloid peptide and diminish the release of [Ca2+]i-stabilizing, neuroprotective APPss.

False

CitationGPTRetr11498

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Ca2+ homeostasis dysregulation in Alzheimer's disease: a focus on plasma membrane and cell organelles. Abstract of the paper: Emerging evidence indicates that Ca2+ is a vital factor in modulating the pathogenesis of Alzheimer's disease (AD). In healthy neurons, Ca2+ concentration is balanced to maintain a lower level in the cytosol than in the extracellular space or certain intracellular compartments such as endoplasmic reticulum (ER) and the lysosome, whereas this homeostasis is broken in AD. On the plasma membrane, the AD hallmarks amyloid-β (Aβ) and tau interact with ligand-gated or voltage-gated Ca2+-influx channels and inhibit the Ca2+-efflux ATPase or exchangers, leading to an elevated intracellular Ca2+ level and disrupted Ca2+ signal. In the ER, the disabled presenilin "Ca2+ leak" function and the direct implications of Aβ and presenilin mutants contribute to Ca2+-signal disorder. The enhanced ryanodine receptor (RyR)-mediated and inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release from the ER aggravates cytosolic Ca2+ disorder and triggers apoptosis; the down-regulated ER Ca2+ sensor, stromal interaction molecule (STIM), alleviates store-operated Ca2+ entry in plasma membrane, leading to spine loss. The increased transfer of Ca2+ from ER to mitochondria through mitochondria-associated ER membrane (MAM) causes Ca2+ overload in the mitochondrial matrix and consequently opens the cellular damage-related channel, mitochondrial permeability transition pore (mPTP). In this review, we discuss the effects of Aβ, tau and presenilin on neuronal Ca2+ signal, focusing on the receptors and regulators in plasma membrane and ER; we briefly introduce the involvement of MAM-mediated Ca2+ transfer and mPTP opening in AD pathogenesis.-Wang, X., Zheng, W. Ca2+ homeostasis dysregulation in Alzheimer's disease: a focus on plasma membrane and cell organelles.

False

CitationGPTRetr11499

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiple studies have demonstrated that aβ can dysregulate ca2 homeostasis via several ca2 signaling components calcineurin nmdars ampars and pqtype vgccs Title of the paper: Glial calcium signalling in Alzheimer's disease. Abstract of the paper: The most accredited (and fashionable) hypothesis of the pathogenesis of Alzheimer Disease (AD) sees accumulation of β-amyloid protein in the brain (in both soluble and insoluble forms) as a leading mechanism of neurotoxicity. How β-amyloid triggers the neurodegenerative disorder is at present unclear, but growing evidence suggests that a deregulation of Ca(2+) homeostasis and deficient Ca(2+) signalling may represent a fundamental pathogenic factor. Given that symptoms of AD are most likely linked to synaptic dysfunction (at the early stages) followed by neuronal loss (at later and terminal phases of the disease), the effects of β-amyloid have been mainly studied in neurones. Yet, it must be acknowledged that neuroglial cells, including astrocytes, contribute to pathological progression of most (if not all) neurological diseases. Here, we review the literature pertaining to changes in Ca(2+) signalling in astrocytes exposed to exogenous β-amyloid or in astrocytes from transgenic Alzheimer disease animals models, characterized by endogenous β-amyloidosis. Accumulated experimental data indicate deregulation of Ca(2+) homeostasis and signalling in astrocytes in AD, which should be given full pathogenetic consideration. Further studies are warranted to comprehend the role of deficient astroglial Ca(2+) signalling in the disease progression.

False