title: Ferulic acid destabilizes preformed beta-amyloid fibrils in vitro.
abstract: 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 curcumin (Cur) inhibits fAbeta formation from Abeta and destabilizes preformed fAbeta in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) 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 FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependently inhibited fAbeta formation from amyloid beta-peptide, as well as their extension. Moreover, it destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of: Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Mie
authors.initials: M
authors.lastname: Hirohata
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000682:Amyloid; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000737:chemistry* / Q000648:ultrastructure*; D003373:Coumaric Acids / Q000737:chemistry*; D004355:Drug Stability; D046912:Multiprotein Complexes / Q000032:analysis / Q000737:chemistry / Q000648:ultrastructure; D011487:Protein Conformation; D011489:Protein Denaturation
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D046912:Multiprotein Complexes; C004999:ferulic acid