Complement C3a receptor antagonist attenuates tau hyperphosphorylation via glycogen synthase kinase 3 β signaling pathways.

In this study, we found that exposure of SH-SY5Y cells to okadaic acid (OA) decreased cell viabilities and induced tau hyperphosphorylation. These effects were alleviated by C3a receptor antagonist SB290157 and were further validated by C3a receptor siRNA in OA-treated SH-SY5Y cells. In addition, our results demonstrated that SB290157 markedly inhibited the activities of glycogen synthase kinase 3β (GSK3β), but had no effect on protein phosphatase 2AC subunit (PP2Ac) and cyclin-dependent kinases 5 (CDK5). Our findings here indicate the unique role of the C3a receptor in regulating tau phosphorylation via GSK3β signaling pathways and suggest that the C3a receptor may be a viable target for treating AD.
PMID: 30771350 [PubMed - as supplied by publisher]

Source: European Journal of Pharmacology - February 13, 2019 Category: Drugs & Pharmacology Authors: Hu J, Yang Y, Wang M, Yao Y, Chang Y, He Q, Ma R, Li G Tags: Eur J Pharmacol Source Type: research