http://www.blackwell-synergy.com/doi...9.2006.03707.x
J Neurochem. 2006 Apr;97(1):105-15. Epub 2006 Mar 8. Links
Antioxidant compounds have potent anti-fibrillogenic and fibril-
destabilizing effects for alpha-synuclein fibrils in vitro.Ono K,
Yamada M.
Department of Neurology and Neurobiology of Aging, Kanazawa University
Graduate School of Medical Science, Kanazawa, Japan.
The aggregation of alpha-synuclein (alphaS) in the brain has been
implicated as a critical step in the development of Lewy body diseases
(LBD) and multiple system atrophy (MSA). Various antioxidants not only
inhibit the formation of beta-amyloid fibrils (fAbeta), but also
destabilize preformed fAb in vitro. Using fluorescence spectroscopy
with thioflavin S and electron microscopy, here we examined the
effects of the antioxidants nordihydroguaiaretic acid, curcumin,
rosmarinic acid, ferulic acid, wine-related polyphenols [tannic acid,
myricetin, kaempferol (+)-catechin and (-)-epicatechin],
docosahexaenoic acid, eicosapentaenoic acid, rifampicin and
tetracycline on the formation of alphaS fibrils (falphaS) and on
preformed falphaS. All molecules, except for docosahexaenoic acid and
eicosapentaenoic acid, dose-dependently inhibited the formation of
falphaS. Moreover, these molecules dose-dependently destabilized
preformed falphaS. The overall activity of the molecules examined was
in the order of: tannic acid=nordihydroguaiaretic
acid=curcumin=rosmarinic acid=myricetin>kaempferol=ferulic acid>(+)-
catechin=(-)-epicatechin>rifampicin=tetracycline. These compounds with
anti-fibrillogenic as well as antioxidant activities could be key
molecules for the development of preventives and therapeutics for LBD
and MSA as well as Alzheimer's disease.