SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease

Serine-arginine protein kinases 2 (SRPK2) is a cell cycle-regulated kinase that phosphorylates serine/arginine domain-containing proteins and mediates pre-mRNA splicing with unclear function in neurons. Here, we show that SRPK2 phosphorylates tau on S214, suppresses tau-dependent microtubule polymerization, and inhibits axonal elongationin neurons. DepletionofSRPK2in dentate gyrus inhibits tau phosphorylation in APP/PS1 mouse and alleviates the impaired cognitive behaviors. The defective LTP in APP/PS1 mice is also improved after SRPK2 depletion. Moreover, active SRPK2isincreasedinthe cortexof APP/PS1 mice and the pathological structures of human Alzheimer's disease (AD) brain. Therefore, our study suggestsSRPK2may contributetothe formationofhyperphosphorylated tau and the pathogenesis of AD.