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

被引：64

作者：

Pei, Lei ^{[1
,4
]}

Wang, Shan ^{[2
,4
]}

Jin, Huijuan ^{[2
,4
]}

Bi, Linlin ^{[2
,4
]}

Wei, Na ^{[2
,4
]}

Yan, Honglin ^{[2
,4
]}

Yang, Xin ^{[2
,4
]}

Yao, Chengye ^{[2
,4
]}

Xu, Mengmeng ^{[2
,4
]}

Shu, Shu ^{[2
,4
]}

Guo, Yu ^{[2
,4
]}

Yan, Huanhuan ^{[2
,4
]}

Wu, Jianhua ^{[2
,4
]}

Li, Hao ^{[2
,4
]}

Pang, Pei ^{[2
,4
]}

Tian, Tian ^{[2
,4
]}

Tian, Qing ^{[3
,4
]}

Zhu, Ling-Qiang ^{[3
,4
]}

Shang, You ^{[4
,5
]}

Lu, Youming ^{[2
,4
,5
]}

机构：

[1] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Neurobiol, Wuhan 430030, Peoples R China

[2] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Physiol, Wuhan 430030, Peoples R China

[3] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathophysiol, Wuhan 430030, Peoples R China

[4] Huazhong Univ Sci & Technol, Collaborat Innovat Ctr Brain Sci, Inst Brain Res, Wuhan 430030, Peoples R China

[5] Union Hosp, Inst Anesthesia & Crit Care, Dept Crit Care Med, Wuhan, Peoples R China

来源：

CEREBRAL CORTEX | 2015年 / 25卷 / 11期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

DAPK1; dendritic spine; stroke; tau phosphorylation; therapeutics; ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; PROTEIN; PHOSPHORYLATION; DEGENERATION; BRAIN; DEATH; RAT; TAUOPATHIES; HYPOXIA;

D O I：

10.1093/cercor/bhv096

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

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 (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.

引用

页码：4559 / 4571

页数：13

共 31 条

[1] Cellular oxygen sensing need in CNS function: physiological and pathological implications [J].