title: The anti-amyloidogenic effect is exerted against Alzheimer's beta-amyloid fibrils in vitro by preferential and reversible binding of flavonoids to the amyloid fibril structure.
abstract: How various anti-amyloidogenic compounds inhibit the formation of Alzheimer's beta-amyloid fibrils (fAbeta) from amyloid beta-peptide (Abeta) and destabilize fAbeta remains poorly understood. Using spectrophotometry, spectrofluorometry, atomic force microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and surface plasmon resonance (SPR), we investigated the anti-amyloidogenic effects of five flavonoids on fAbeta in vitro. Oxidized flavonoids generally inhibited fAbeta(1-40) formation significantly more potently than fresh compounds. Characterization of the novel fluorescence of myricetin (Myr) emitted at 575 nm with an excitation maximum at 430 nm in the presence of fAbeta(1-40) revealed the specific binding of Myr to fAbeta(1-40). By SPR analysis, distinct association and dissociation reactions of Myr with fAbeta(1-40) were observed, in contrast to the very weak binding to the Abeta monomer. A significant decrease in the rate of fibril extension was observed when >0.5 microM Myr was injected into the SPR experimental system. These findings suggest that flavonoids, especially Myr, exert an anti-amyloidogenic effect in vitro by preferentially and reversibly binding to the amyloid fibril structure of fAbeta, rather than to Abeta monomers.
authors.affiliation: Division of Molecular Pathology, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Hirohata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tsutsumi-Yasuhara
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ohhashi
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Ookoshi
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005419:Flavonoids / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry / Q000379:methods; D020349:Surface Plasmon Resonance
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D005419:Flavonoids; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)