title: Crocetin inhibits beta-amyloid fibrillization and stabilizes beta-amyloid oligomers.
abstract: Aggregation of a peptide, beta-amyloid (Aβ), is a hallmark molecular process found in Alzheimer's disease (AD). During Aβ aggregation, oligomeric and fibrillar Aβ are formed, and these molecular self-assembly steps are implicated in generation of toxic effects in AD. Crocetin is a natural carotenoid dicarboxyl acid displaying various pharmaceutical effects and may be co-localized with Aβ mediated by human serum albumin. In the study presented here, we examined the effects of crocetin on Aβ aggregation in three different molecular pathways. Our results demonstrate that crocetin inhibited Aβ fibril formation and destabilized pre-formed Aβ fibrils. Moreover, crocetin caused stabilization of Aβ oligomers and prevented their conversion into Aβ fibrils. Our study reveals potential pathological and pharmaceutical implication of crocetin in AD and suggests possible application of crocetin for currently limited structural studies on unstable Aβ oligomers.
authors.affiliation: Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201, USA.
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Ahn
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Michael
authors.initials: M
authors.lastname: Hernandez
authors.forename: Jin Ryoun
authors.initials: JR
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D052160:Benzothiazoles; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D005453:Fluorescence; D006801:Humans; D008969:Molecular Sequence Data; D013844:Thiazoles / Q000737:chemistry; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D013844:Thiazoles; C487773:trans-sodium crocetinate; D014801:Vitamin A; C009462:thioflavin T; D002338:Carotenoids