Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease
Version of Record online: 12 SEP 2003
Journal of Neurochemistry
Volume 87, Issue 1, pages 172–181, October 2003
How to Cite
Ono, K., Yoshiike, Y., Takashima, A., Hasegawa, K., Naiki, H. and Yamada, M. (2003), Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease. Journal of Neurochemistry, 87: 172–181. doi: 10.1046/j.1471-4159.2003.01976.x
- Issue online: 12 SEP 2003
- Version of Record online: 12 SEP 2003
- Received May 5, 2003; revised manuscript received June 19, 2003; accepted June 20, 2003.
- Alzheimer's disease;
- β-amyloid fibrils;
- electron microscopy;
- thioflavin T
Cerebral deposition of amyloid β-peptide (Aβ) in the brain is an invariant feature of Alzheimer's disease (AD). A consistent protective effect of wine consumption on AD has been documented by epidemiological studies. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of wine-related polyphenols (myricetin, morin, quercetin, kaempferol (+)-catechin and (–)-epicatechin) on the formation, extension, and destabilization of β-amyloid fibrils (fAβ) at pH 7.5 at 37°C in vitro. All examined polyphenols dose-dependently inhibited formation of fAβ from fresh Aβ(1–40) and Aβ(1–42), as well as their extension. Moreover, these polyphenols dose-dependently destabilized preformed fAβs. The overall activity of the molecules examined was in the order of: myricetin = morin = quercetin > kaempferol > (+)-catechin = (–)-epicatechin. The effective concentrations (EC50) of myricetin, morin and quercetin for the formation, extension and destabilization of fAβs were in the order of 0.1–1 µm. In cell culture experiments, myricetin-treated fAβ were suggested to be less toxic than intact fAβ, as demonstrated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Although the mechanisms by which these polyphenols inhibit fAβ formation from Aβ, and destabilize pre-formed fAβin vitro are still unclear, polyphenols could be a key molecule for the development of preventives and therapeutics for AD.