Two Faces of Evil: Cancer and Neurodegeneration [electronic resource] /
Curran, Thomas.editor.
Christen, Yves.editor.
The two greatest medical fears of the aging population are cancer and Alzheimer's disease. Despite dramatic advances in understanding the molecular etiology of these disorders, therapeutic options for many patients with advanced disease have changed little and outcomes remain dismal. Paradoxically, recent findings suggest that some of the same molecules and biochemical processes underlying cancer may also participate in neurodegeneration. Therefore, it would be very useful to bring together experts from the fields of cancer research and neurodegeneration for discussions of the latest advances and ideas, with a particular emphasis on areas of overlap, to stimulate transdisciplinary interactions with the hope of accelerating progress. Cancer arises as a consequence of a breakdown in the genetic and epigenetic processes governing cell proliferation and cell death. Alterations in several classes of signaling molecules, both oncogenes and tumor suppressor genes, lead to uncontrolled cell growth. Over the past two decades, details of the intricate signaling pathways, from cell surface receptors through protein kinase cascades, transcription factors and modulators of chromatin, as well as the DNA damage response pathways linked to cell cycle control that guard the genome, have been uncovered. In some instances, key regulatory proteins have provided novel targets for development of small molecule inhibitors that are currently being tested in the clinic. The development of the nervous system relies on many of the signaling pathways and growth control processes that go awry in cancer. However, in mature neurons, the very same signaling proteins participate in transduction cascades linking short-term stimuli, elicited by synaptic stimulation, to long-term alterations in neuronal circuits through the regulation of gene expression and chromatin structure. These long-term adaptive modifications lead to changes in synaptic structure and function that contribute to learning and memory. The persistence of growth regulatory molecules in postmitotic neurons provides an opportunity for their contribution to pathophysiological processes resulting in neuronal loss. Recently, evidence has accumulated suggesting an association of cell cycle proteins and signal transduction proteins with neurodegeneration. Indeed, inhibitors of histone deacetylation have shown promise both as anti-cancer agents and in the prevention of neuronal loss.
Description based upon print version of record.
Two Faces of Evil: Cancer and Neurodegeneration; Foreword; Acknowledgments; Contents; Contributors; Updating the Mammalian Cell Cycle: The Role of Interphase Cdks in Tissue Homeostasis and Cancer; 1 Mammalian Cdks and the Classical Cell Cycle Model; 2 Interphase Cdks are Not Essential for the Mammalian Cell Cycle; 3 Limited Compensatory Activities Among Interphase Cdks; 4 Interphase Cdks Have Evolved to Drive Proliferation of Highly Specialized Cells; 5 Cell Cycle Cdks and Cancer; 6 Are Interphase Cdks Required for Tumor Development?; References
The Role of Cdk5 as a Cell Cycle Suppressor in Post-mitotic Neurons1 Introduction; 2 Cdk5 Plays an Important Role in Neuronal Development; 3 Cdk5 Serves Important Functions in the Regulation of Synaptic Function; 4 Cdk5 is a Cell Cycle Suppressor in Post-mitotic Neurons; 5 Cdk5 Inhibits the Cell Cycle in a Kinase-Independent Fashion; 6 Cdk5 Inhibits the Cell Cycle by Sequestering E2F1; 7 The Implications of the Central Role of Cdk5 in Neuronal Cell Cycle Suppression; References; Actin-SRF Signaling in the Developing and Mature Murine Brain; 1 Principles of Actin-SRF Signaling in Brain Cells
1.1 Actin Dynamics Regulates Gene Expression Upon Activation of MRTF-SRF Signaling1.2 Actin Dynamics in Neuronal Network Assembly; 1.3 Actin-MRTF-SRF interplay in Neuronal Signaling; 2 Essential functions of SRF and MRTF in Mouse Brain Development; 2.1 Embryonic Neuronal Migration; 2.2 Axonal Outgrowth, Guidance, and Synaptic Targeting; 3 Functional Actin-SRF Interplay in the Mature Brain; 3.1 Activity-Induced Gene Expression; 3.2 Learning and Memory; 4 Linking SRF to Neurodegenerative Diseases, Psychiatric Disorders, and Addiction
4.1 SRF Protects Against Axonal De-myelination and Degeneration4.2 SRF and Epileptic Seizure-Induced Neuronal IEG Expression; 4.3 SRF in M. Alzheimer; 4.4 SRF as a Novel Player in Addictive Behavior and Hyperactive Disorder; References; The E3 Ubiquitin Ligase Ube3A Regulates Synaptic Function Through the Ubiquitination of Arc; 1 A Role for Ube3A in Human Disorders of Cognitive Function; 2 Ube3a is a Neuronal Activity-Regulated Gene; 3 Regulation of Synaptic AMPA Receptor Function by Ube3A; 4 A Novel Proteomic Approach to Ube3A Substrate Identification
5 Arc is a Neuronal Ube3A Substrate that Mediates the Effect of Ube3A on AMPAR Trafficking6 Discussion; References; Targeting Children ́s Brain Tumors: Development of Hedgehog Pathway Inhibitors for Medulloblastoma; 1 Introduction; 2 Role of the Hh Pathway in Medulloblastoma; 3 Targeting Smoothened; 4 Hh Pathway is Downregulated in Tumor Cell Lines; 5 Direct Allografts Retain Hh Pathway Activity; 6 Testing Targeted Therapies in Mice; 7 HhAntag Eradicates Large Tumors in PtchI+/-p53-/- Mice; 8 Hh Pathway Inhibition Causes Bone Defects in Young Mice; 9 Inhibiting the Hh Pathway in the Clinic
References
Includes bibliographical references and index.
The two greatest medical fears of the aging population are cancer and Alzheimer's disease. Despite dramatic advances in understanding the molecular etiology of these disorders, therapeutic options for many patients with advanced disease have changed little and outcomes remain dismal. Paradoxically, recent findings suggest that some of the same molecules and biochemical processes underlying cancer may also participate in neurodegeneration. Therefore, it would be very useful to bring together experts from the fields of cancer research and neurodegeneration for discussions of the latest advances and ideas, with a particular emphasis on areas of overlap, to stimulate transdisciplinary interactions with the hope of accelerating progress. Cancer arises as a consequence of a breakdown in the genetic and epigenetic processes governing cell proliferation and cell death. Alterations in several classes of signaling molecules, both oncogenes and tumor suppressor genes, lead to uncontrolled cell growth. Over the past two decades, details of the intricate signaling pathways, from cell surface receptors through protein kinase cascades, transcription factors and modulators of chromatin, as well as the DNA damage response pathways linked to cell cycle control that guard the genome, have been uncovered. In some instances, key regulatory proteins have provided novel targets for development of small molecule inhibitors that are currently being tested in the clinic. The development of the nervous system relies on many of the signaling pathways and growth control processes that go awry in cancer. However, in mature neurons, the very same signaling proteins participate in transduction cascades linking short-term stimuli, elicited by synaptic stimulation, to long-term alterations in neuronal circuits through the regulation of gene expression and chromatin structure. These long-term adaptive modifications lead to changes in synaptic structure and function that contribute to learning and memory. The persistence of growth regulatory molecules in postmitotic neurons provides an opportunity for their contribution to pathophysiological processes resulting in neuronal loss. Recently, evidence has accumulated suggesting an association of cell cycle proteins and signal transduction proteins with neurodegeneration. Indeed, inhibitors of histone deacetylation have shown promise both as anti-cancer agents and in the prevention of neuronal loss.
Neurosciences.
Cancer research.
Neurosciences.
Cancer Research.
Research and perspectives in Alzheimer's disease