Polyphenols and neurodegenerative diseases

Flavonoids are naturally occurring polyphenolic compounds that are present in a variety of fruits, vegetables, cereals, tea, and wine, and are the most abundant antioxidants in the human diet. In this special issue, the articles aim to cover recent advancement of various approaches, mainly those from dietary and nutraceutical sources, biological models, and molecular mechanisms relevant to the neuroprotective role of flavonoids polyphenolics, as natural antioxidant compounds, on excitability-related neurological disorders (like migraine and epilepsy), and neurodegenerative diseases. These include Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis Huntington’s disease, and also traumatic brain injury and brain ischaemia. There is a growing interest on this topic, as neuroprotection by flavonoids present in plants and foods have been widely described and could potentially be applied to clinical studies to improve the outcome after any type of brain insult. Not only in vivo studies but also in vitro studies could benefit from using these compounds, which have shown to be an important asset in detoxifying or protecting cells against different toxicological paradigms. More recently, research has attempted to identify novel polyphenols from natural plant extracts with antioxidant properties. Some examples are, but not limited to, flavones (apigrin, luteolin, etc.), flavonols (quecertin, such as rutin, etc), flavonones (hesperitin), flavonols and their polymers (catechin, epicatechin, etc), isoflavones phytoestrogens, stillbenoids (resveratrol) and anthocyanins. Therefore, this topic is very exciting, as this could be turned out to a more clinical-oriented study; however, we still have a great lack of information on the real potential role of these antioxidants in some damaging conditions, as well as on experimental models. A variety of in vivo approaches include the development of novel central nervous system (CNS) agents and ground-breaking strategies for genetically targeted antioxidant molecules, stem cell and micro RNA therapeutics. All the treatments target either the mechanisms or the mediators leading to brain injuries in vivo and/or cytotoxicity in vitro. Mechanisms including apoptosis, necrosis, autophagy, inflammation, and mediators like various excitatory amino acids, nitric oxide, inflammatory mediators, neurotransmitters, reactive oxygen species, and withdrawal of trophic factors may lead to development of ischaemic and haemorrhagic strokes, traumatic brain injury, and neonatal hypoxia–ischemic brain injury, excitotoxic, and infectious damage. Likewise, in this issue, articles focused on up-to-date research on flavonoids neuroprotective agents from foods and plants targeting these pathways and mediators leading to CNS damage. The articles published in this special issue have shed light on important topics related to polyphenols and neurodegeneration. They summarize the current advances on in vivo animal models, in vitro cellular models, and ex vivo organotypic/acute brain slice models currently available for studying CNS injuries, and apply the best antioxidant therapy to ameliorate the associated neurological damage. Also current progress in imaging techniques and improved surgical procedures, as well as ongoing human trials of antioxidant agents, is discussed. In the first part of this special issue, we addressed the role of oxidative stress (Madureira de Oliveira et al.), early ubiquitination and changes in synaptic transmission (Grimaldi et al.), as an early pathological event that likely occurs in the onset of a neurodegenerative disease. From this initial characterization of biochemical, physiological and pathological events that precede degeneration, we focused on the most used polyphenols as neuroprotective compound against a variety of insults (Albarracin et al. published in January 2012 issue), such as mitochondrial oxidative stress (Linseman, published in November 2011 issue), cortical spreading depression (Guedes et al.), Parkinson (Sutachan et al.), psychiatric and cognitive disorders (Gomez-Pinilla and Nguyen) and dementia (Ho et al. published in January 2012 issue). It is important to point that some possible neuroprotective