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Ferulic acid inhibits the transition of amyloid-β42 monomers to oligomers but accelerates the transition from oligomers to fibrils.
|Title||Ferulic acid inhibits the transition of amyloid-β42 monomers to oligomers but accelerates the transition from oligomers to fibrils.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Cui L, Zhang Y, Cao H, Wang Y, Teng T, Ma G, Li Y, Li K, Zhang Y|
|Journal||Journal of Alzheimer's disease : JAD|
|Date Published||2013 Jan 1|
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.
|Alternate Journal||J. Alzheimers Dis.|