4.7 Article

SRPK2 Phosphorylates Tau and Mediates the Cognitive Defects in Alzheimer's Disease

Journal

JOURNAL OF NEUROSCIENCE
Volume 32, Issue 48, Pages 17262-17272

Publisher

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3300-12.2012

Keywords

-

Categories

Funding

  1. NCI, NIH [NS060680]
  2. NIA, NIH [AG028679]

Ask authors/readers for more resources

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 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available