title: Antioxidant compounds have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro.
abstract: 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.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid*; D008297:Male; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D051844:alpha-Synuclein / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D051844:alpha-Synuclein