The polyphenol piceid destabilizes preformed amyloid fibrils and oligomers in vitro: hypothesis on possible molecular mechanisms.
Alzheimer's disease (AD) is characterized by deposits of amyloid in various tissues. The neuronal cytotoxicity of Abeta peptides is attributed not only to various mechanisms but also to amyloid fibrils and soluble oligomeric intermediates. Consequently, finding molecules to prevent or reverse the oligomerization and fibrillization of Abeta could be of therapeutic value in the treatment of AD. We show that piceid, a polyphenol of the stilbene family, destabilized fibrils and oligomers to give back monomers that are not neurotoxic molecules. The mechanism of this destabilization could be a dynamic interaction between the polyphenol and the Abeta that could open the hydrophobic zipper and shift the reversible equilibrium "random coil<-->beta-sheet" to the disordered structure.
Rivière
Céline
C
Laboratoire de physique et biophysique, GESVAB EA 3675, ISVV, Université de Bordeaux 2, Bordeaux cedex, France.
Delaunay
Jean-Claude
JC
Immel
Françoise
F
Cullin
Christophe
C
Monti
Jean-Pierre
JP
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D052160:Benzothiazoles; D002850:Chromatography, Gel; D005419:Flavonoids / Q000737:chemistry*; D005456:Fluorescent Dyes; D005960:Glucosides / Q000737:chemistry*; D006801:Humans; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D059808:Polyphenols; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013267:Stilbenes / Q000737:chemistry*; D013844:Thiazoles
D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005419:Flavonoids; D005456:Fluorescent Dyes; D005960:Glucosides; D009842:Oligopeptides; D010446:Peptide Fragments; D010636:Phenols; D059808:Polyphenols; D013267:Stilbenes; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); C009462:thioflavin T; C058229:polydatin