Objective: To investigate the role and mechanism of C3a receptor in okadaic acid（OA） induced SH-SY5Y cells tau hyperphosphorylation model

Background: Neurofibrillary tangles aggregated from hyperphosphorylated tau protein are the main pathological feature of Alzheimer’s disease (AD). Complement C3 (or C3a) is the core component of the complement system and is associated with AD pathological processes. Although C3/C3a receptors have been proved to participate in Aβ plaque pathology, effects on tau phosphorylation remain unclear.

Method: SH-SY5Y cells were pretreated with C3a receptor antagonist SB290157 or control for 24 h and then exposed to OA for 12 h. SiRNA interference were performed by treating the cells with with C3aR SiRNA or control SiRNA. After transfection, SHSY5Y cells were exposed to OA. After these treatments, cells were used for biochemical analysis.

Results: 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 2A C subunit (PP2Ac) and cyclin-dependent kinases 5 (CDK5).

Conclusion: Our findings here indicate the 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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/complement-c3a-receptor-antagonist-attenuates-tau-hyperphosphorylation-via-glycogen-synthase-kinase-3%ce%b2-signaling-pathways/