Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: implications for neurodegenerative diseases.
Accumulating evidence supports the hypothesis that brain iron misregulation and oxidative stress (OS), resulting in reactive oxygen species (ROS) generation from H2O2 and inflammatory processes, trigger a cascade of events leading to apoptotic/necrotic cell death in neurodegenerative disorders, such as Parkinson's (PD), Alzheimer's (AD) and Huntington's diseases, and amyotrophic lateral sclerosis (ALS). Thus, novel therapeutic approaches aimed at neutralization of OS-induced neurotoxicity, support the application of ROS scavengers, transition metals (e.g. iron and copper) chelators and non-vitamin natural antioxidant polyphenols, in monotherapy, or as part of antioxidant cocktail formulation for these diseases. Both experimental and epidemiological evidence demonstrate that flavonoid polyphenols, particularly from green tea and blueberries, improve age-related cognitive decline and are neuroprotective in models of PD, AD and cerebral ischemia/reperfusion injuries. However, recent studies indicate that the radical scavenger property of green tea polyphenols is unlikely to be the sole explanation for their neuroprotective capacity and in fact, a wide spectrum of cellular signaling events may well account for their biological actions. In this article, the currently established mechanisms involved in the beneficial health action and emerging studies concerning the putative novel molecular neuroprotective activity of green tea and its major polyphenol (-)-epigallocatechin-3-gallate (EGCG), will be reviewed and discussed.
Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Technion-Faculty of Medicine, Haifa, Israel.
Silvia
S
Mandel
Orly
O
Weinreb
Tamar
T
Amit
Moussa B H
MB
Youdim
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013662:Tea
D005419:Flavonoids; D018696:Neuroprotective Agents; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate