학술논문

SRPK2 Phosphorylates Tau and Mediates the Cognitive Defects in Alzheimer's Disease.
Document Type
Article
Source
Journal of Neuroscience. 11/28/2012, Vol. 32 Issue 48, p17262-17272. 11p.
Subject
*PROTEIN kinases
*CELL cycle regulation
*PHOSPHORYLATION
*TAU proteins
*MICROTUBULES
*POLYMERIZATION
*ALZHEIMER'S disease
*LABORATORY mice
*PHYSIOLOGY
*THERAPEUTICS
Language
ISSN
0270-6474
Abstract
Serine-arginine protein kinases 2 (SRPK2) is a cell cycle-regulated kinase that phosphorylates serine/arginine domain-containing pro-teins 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 elongation in neurons. Depletion of SRPK2 in 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 SRPK2 is increased in the cortex of APP/PS1 mice and the pathological structures of human Alzheimer's disease (AD) brain. Therefore, our study suggests SRPK2 may contribute to the formation of hyperphosphorylated tau and the pathogenesis of AD. [ABSTRACT FROM AUTHOR]