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Antioxidant compounds have potent anti‐fibrillogenic and fibril‐destabilizing effects for α‐synuclein fibrils in vitro
Author(s) -
Ono Kenjiro,
Yamada Masahito
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03707.x
Subject(s) - chemistry , myricetin , ferulic acid , rosmarinic acid , curcumin , biochemistry , caffeic acid , antioxidant , kaempferol , quercetin
The aggregation of α‐synuclein (αS) 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 β‐amyloid fibrils (fAβ), 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 αS fibrils (fαS) and on preformed fαS. All molecules, except for docosahexaenoic acid and eicosapentaenoic acid, dose‐dependently inhibited the formation of fαS. Moreover, these molecules dose‐dependently destabilized preformed fαS. 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.