DAPK1与Tau蛋白介导脑卒中突触棘损伤的新机制-武汉天德生物科技有限公司

Cereb Cortex. 2015 May 20;25(11):4559–4571. doi: 10.1093/cercor/bhv096

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

期刊: Cerebral Cortex	发表时间: 2015-05-20	影响因子:
作者列表: Lei Pei ^1,^4,^†, Shan Wang ^2,^4,^†, Huijuan Jin ^2,⁴, Linlin Bi ^2,⁴, Na Wei ^2,⁴, Honglin Yan ^2,⁴, Xin Yang ^2,⁴, Chengye Yao ^2,⁴, Mengmeng Xu ^2,⁴, Shu Shu ^2,⁴, Yu Guo ^2,⁴, Huanhuan Yan ^2,⁴, Jianhua Wu ^2,⁴, Hao Li ^2,⁴, Pei Pang ^2,⁴, Tian Tian ^2,⁴, Qing Tian ^3,⁴, Ling-Qiang Zhu ^3,⁴, You Shang ^4,⁵, Youming Lu ^2,^4,⁵
第一作者国家: 中国	第一作者单位: 华中科技大学同济医学院
通讯作者国家: 中国	通讯作者单位: 华中科技大学同济医学院

研究领域：树突棘损伤中风 DAPK1 Tau蛋白磷酸化神经元死亡小鼠模型基因敲除膜渗透肽神经功能

关键字：神经科学分子生物学神经病学

摘要

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 (pS262) 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.

该研究中，武汉百意欣生物科技有限公司（现武汉天德生物科技有限公司）协助提供多肽合成服务。