title: A Novel Mechanism of Spine Damages in Stroke via DAPK1 and Tau.
abstract: 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.
authors.affiliation: Department of Neurobiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Pei
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chengye
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Shu
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Pang
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ling-Qiang
authors.initials: LQ
authors.lastname: Zhu
authors.affiliation: The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Wuhan, China.
authors.forename: You
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Department of Physiology, School of Basic Medicine The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Wuhan, China.
authors.forename: Youming
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology; D064550:Death-Associated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009460:Neurologic Examination; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D010455:Peptides / Q000627:therapeutic use; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D020521:Stroke / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D010455:Peptides; D016875:tau Proteins; C579106:Dapk1 protein, mouse; D064550:Death-Associated Protein Kinases; D010751:Phosphopyruvate Hydratase
keywords: DAPK1; dendritic spine; stroke; tau phosphorylation; therapeutics