Abstract:
: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. However, it remains unclear whether C3a or the C3a receptor has any effect on tau phosphorylation. 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). 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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Hu J,Yang Y,Wang M,Yao Y,Chang Y,He Q,Ma R,Li Gdoi
10.1016/j.ejphar.2019.02.020subject
Has Abstractpub_date
2019-05-05 00:00:00pages
135-140eissn
0014-2999issn
1879-0712pii
S0014-2999(19)30113-Xjournal_volume
850pub_type
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