Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease.
Regulated neuronal cell death plays an essential role in biological processes in normal physiology, including the development of the nervous system. However, the deregulation of neuronal apoptosis by various factors leads to neurodegenerative diseases such as ischemic stroke and Alzheimer's disease (AD). Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca2+/CaM)-dependent serine/threonine (Ser/Thr) protein kinase that activates death signaling and regulates apoptotic neuronal cell death. Although DAPK1 is tightly regulated under physiological conditions, DAPK1 deregulation in the brain contributes to the development of neurological disorders. In this review, we describe the molecular mechanisms of DAPK1 regulation in neurons under various stresses. We also discuss the role of DAPK1 signaling in the phosphorylation-dependent and phosphorylation-independent regulation of its downstream targets in neuronal cell death. Moreover, we focus on the major impact of DAPK1 deregulation on the progression of neurodegenerative diseases and the development of drugs targeting DAPK1 for the treatment of diseases. Therefore, this review summarizes the DAPK1 phosphorylation signaling pathways in various neurodegenerative diseases.
['Kim|Nami|N|', 'Chen|Dongmei|D|', 'Zhou|Xiao Zhen|XZ|', 'Lee|Tae Ho|TH|']
D000544:Alzheimer Disease D000818:Animals D017209:Apoptosis D015415:Biomarkers D016923:Cell Death D064550:Death-Associated Protein Kinases D006801:Humans D005810:Multigene Family D019636:Neurodegenerative Diseases D009474:Neurons D010766:Phosphorylation D020521:Stroke D013329:Structure-Activity Relationship
phosphorylation neuronal cell death ischemic stroke death-associated protein kinase 1 (DAPK1) Alzheimer’s disease (AD)