Inhibitory activity of stilbenes on Alzheimer's beta-amyloid fibrils in vitro

Bioorg Med Chem. 2007 Jan 15;15(2):1160-7. doi: 10.1016/j.bmc.2006.09.069. Epub 2006 Oct 1.

Abstract

Polymerization of the amyloid beta-peptide (Abeta) has been identified as one of the major characteristics of Alzheimer's disease (AD). Thus, finding molecules to prevent the aggregation of Abeta could be of therapeutic value in AD. We describe an original routine in vitro assay to search for inhibitors of Abeta(25-35) fibril formation which uses UV-visible measurements and electron microscopy (EM). In particular, this routine assay was used to examine the effects of stilbenes, a well-known polyphenol class, as inhibitors of Abeta fibril formation. The inhibitory properties of resveratrol (RES), piceid (PIC), resveratrol diglucoside (DIG), piceatannol (PIA), astringine (AST), and viniferin (VIN) were characterized and compared. RES and PIC effectively and dose-dependently inhibited Abeta polymerization while other polyphenols exerted less inhibition. Although the mechanism of anti-amyloidogenic activity is still unknown, these results support the hypothesis that stilbenes could be of therapeutic value in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / drug effects*
  • Amyloid beta-Peptides / pharmacology
  • Amyloid beta-Peptides / toxicity
  • Amyloid beta-Peptides / ultrastructure
  • Animals
  • Bradykinin / chemical synthesis
  • Bradykinin / pharmacology
  • Curcumin / pharmacology
  • Microscopy, Electron
  • PC12 Cells
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology
  • Peptide Fragments / toxicity
  • Polymers / chemical synthesis
  • Rats
  • Solutions
  • Spectrophotometry, Ultraviolet
  • Stilbenes / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Polymers
  • Solutions
  • Stilbenes
  • amyloid beta-protein (25-35)
  • Curcumin
  • Bradykinin