Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid-Beta Peptides

J Biol Chem. 2005 Nov 11;280(45):37377-82. doi: 10.1074/jbc.M508246200. Epub 2005 Sep 14.

Abstract

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 (Abeta) peptides produced from different cell lines. Resveratrol does not inhibit Abeta production, because it has no effect on the Abeta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of Abeta via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Abeta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta5. 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / metabolism*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Cell Line
  • Gene Expression Regulation / drug effects
  • Humans
  • Molecular Structure
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors
  • Quercetin / chemistry
  • Quercetin / pharmacology
  • Resveratrol
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Wine / analysis

Substances

  • Amyloid beta-Peptides
  • Proteasome Inhibitors
  • Stilbenes
  • Catechin
  • Quercetin
  • Proteasome Endopeptidase Complex
  • Resveratrol