Ferulic acid inhibits the transition of amyloid-β42 monomers to oligomers but accelerates the transition from oligomers to fibrils.

TitleFerulic acid inhibits the transition of amyloid-β42 monomers to oligomers but accelerates the transition from oligomers to fibrils.
Publication TypeJournal Article
Year of Publication2013
AuthorsCui L, Zhang Y, Cao H, Wang Y, Teng T, Ma G, Li Y, Li K, Zhang Y
JournalJournal of Alzheimer's disease : JAD
Volume37
Issue1
Pagination19-28
Date Published2013 Jan 1
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.

DOI10.1155/2013/379850
Alternate JournalJ. Alzheimers Dis.