Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 280, Issue 45, Pages 37377-37382Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M508246200
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- NIMH NIH HHS [MH 38623] Funding Source: Medline
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Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimer's disease brain remain to be clearly defined. Here we show that resveratrol ( trans-3,4',5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-beta(A beta) peptides produced from different cell lines. Resveratrol does not inhibit A beta production, because it has no effect on the A beta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of A beta via amechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of A beta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta 5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimer's disease.
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