The Anti-Amyloidogenic Effect Is Exerted against Alzheimer's β-Amyloid Fibrils in Vitro by Preferential and Reversible Binding of Flavonoids to the Amyloid Fibril Structure†
journal contributionposted on 20.02.2007, 00:00 by Mie Hirohata, Kazuhiro Hasegawa, Shinobu Tsutsumi-Yasuhara, Yumiko Ohhashi, Tadakazu Ookoshi, Kenjiro Ono, Masahito Yamada, Hironobu Naiki
How various anti-amyloidogenic compounds inhibit the formation of Alzheimer's β-amyloid fibrils (fAβ) from amyloid β-peptide (Aβ) and destabilize fAβ 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 fAβ in vitro. Oxidized flavonoids generally inhibited fAβ(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 fAβ(1−40) revealed the specific binding of Myr to fAβ(1−40). By SPR analysis, distinct association and dissociation reactions of Myr with fAβ(1−40) were observed, in contrast to the very weak binding to the Aβ monomer. A significant decrease in the rate of fibril extension was observed when >0.5 μM 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 fAβ, rather than to Aβ monomers.