title: Ferulic acid inhibits the transition of amyloid-β42 monomers to oligomers but accelerates the transition from oligomers to fibrils.
abstract: Alzheimer's disease (AD) is neurodegenerative disease that occurs among the aging population and is associated with impaired cognitive function. Amyloid-β (Aβ) oligomers initiate the pathological cascade and represent a neuropathic hallmark of AD. Therefore, an approach that inhibits Aβ aggregation is an attractive therapeutic strategy for the treatment of AD. Ferulic acid (FA) is a phenolic compound that can inhibit Aβ42 fibril-induced cytotoxicity both in vitro and in vivo. However, few studies have demonstrated that FA interacts with Aβ42 oligomers. Here, we investigated whether FA inhibits Aβ42 oligomer-induced cytotoxicity and the effect of FA on Aβ aggregation. Our results showed that FA reduced Aβ42-induced neurotoxicity in SH-SY5Y cells. Moreover, using CD spectroscopy, we found that FA inhibited the formation of the β-sheets that are required for the Aβ42 monomer-to-oligomer transition but accelerated the Aβ42 oligomer-to-fibril transition. These phenomena were confirmed by transmission electron microscopy and thioflavin T fluorescence assay. The docking analysis between FA and Aβ42 monomer showed that FA may inhibit the aggregation of Aβ42 oligomers by blocking the hydrogen bond with the forming β-sheets. Taken together, we have identified a novel phenomenon in which FA inhibits the formation of Aβ42 oligomers while accelerating the transition of Aβ42 oligomers to fibrils, and we have shown that FA protects against Aβ42-induced toxicity in vitro by preventing Aβ42 from forming oligomers.
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Teng
authors.initials: T
authors.lastname: Teng
authors.forename: Guoda
authors.initials: G
authors.lastname: Ma
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
authors.forename: Yingjiu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D001665:Binding Sites / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003373:Coumaric Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D016166:Free Radical Scavengers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C004999:ferulic acid