neurodegenerative disease / iron



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J Neurochem. 2004 Mar;88(6):1555-69. Links

Cell signaling pathways in the neuroprotective actions of
the green tea polyphenol (-)-epigallocatechin-3-gallate:
implications for neurodegenerative diseases.

Mandel S, Weinreb O, Amit T, Youdim MB.

Eve Topf and USA National Parkinson Foundation Centers of
Excellence for Neurodegenerative Diseases Research and
Department of Pharmacology, Technion-Faculty of Medicine,
Haifa, Israel.

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.

PMID: 15009657 [PubMed - in process]

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