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Publication : A Novel Mechanism of Spine Damages in Stroke via DAPK1 and Tau.

First Author  Pei L Year  2015
Journal  Cereb Cortex Volume  25
Issue  11 Pages  4559-71
PubMed ID  25995053 Mgi Jnum  J:256380
Mgi Id  MGI:6115749 Doi  10.1093/cercor/bhv096
Citation  Pei L, et al. (2015) A Novel Mechanism of Spine Damages in Stroke via DAPK1 and Tau. Cereb Cortex 25(11):4559-71
abstractText  Synaptic spine loss is one of the major preceding consequences of stroke damages, but its underlying molecular mechanisms remain unknown. Here, we report that a direct interaction of DAPK1 with Tau causes spine loss and subsequently neuronal death in a mouse model with stroke. We found that DAPK1 phosphorylates Tau protein at Ser262 (pS(262)) in cortical neurons of stroke mice. Either genetic deletion of DAPK1 kinase domain (KD) in mice (DAPK1-KD(-/-)) or blocking DAPK1-Tau interaction by systematic application of a membrane permeable peptide protects spine damages and improves neurological functions against stroke insults. Thus, disruption of DAPK1-Tau interaction is a promising strategy in clinical management of stroke.
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