Inhibitory activity of stilbenes on Alzheimer's beta-amyloid fibrils in vitro.
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.
Rivière
Céline
C
Laboratoire de physique et biophysique, Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France.
Richard
Tristan
T
Quentin
Lysiane
L
Krisa
Stéphanie
S
Mérillon
Jean-Michel
JM
Monti
Jean-Pierre
JP
D000465:Algorithms; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects* / Q000494:pharmacology / Q000633:toxicity / Q000648:ultrastructure; D000818:Animals; D001920:Bradykinin / Q000138:chemical synthesis / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology; D008854:Microscopy, Electron; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011108:Polymers / Q000138:chemical synthesis; D051381:Rats; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013267:Stilbenes / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011108:Polymers; D012996:Solutions; D013267:Stilbenes; C074636:amyloid beta-protein (25-35); D003474:Curcumin; D001920:Bradykinin