Preformed beta-amyloid fibrils are destabilized by coenzyme Q10 in vitro.
Inhibition of the formation of beta-amyloid fibrils (fAbeta), as well as the destabilization of preformed fAbeta in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fAbeta formation from Abeta and destabilize preformed fAbeta in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q(10) (CoQ(10)) on the formation, extension, and destabilization of fAbeta at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of CoQ(10) with NDGA and Myr. CoQ(10) dose-dependently inhibited fAbeta formation from amyloid beta-peptide (Abeta), as well as their extension. Moreover, it destabilized preformed fAbetas. The anti-amyloidogenic effects of CoQ(10) were slightly weaker than those of NDGA and Myr. CoQ(10) could be a key molecule for the development of therapeutics for AD.
Ono
Kenjiro
K
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Hasegawa
Kazuhiro
K
Naiki
Hironobu
H
Yamada
Masahito
M
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D003067:Coenzymes; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D013050:Spectrometry, Fluorescence; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D003067:Coenzymes; D014451:Ubiquinone; C024989:coenzyme Q10