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’...
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doaj-cbf43fbe71e94dd19ae1942408f5e12c2020-11-24T21:27:37ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-06-012013313110.3390/ijms20133131ijms20133131Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative DiseaseNami Kim0Dongmei Chen1Xiao Zhen Zhou2Tae Ho Lee3Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, ChinaDivision of Translational Therapeutics, Department of Medicine and Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, ChinaRegulated 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 (Ca<sup>2+</sup>/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.https://www.mdpi.com/1422-0067/20/13/3131death-associated protein kinase 1 (DAPK1)Alzheimer’s disease (AD)ischemic strokeneuronal cell deathphosphorylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nami Kim Dongmei Chen Xiao Zhen Zhou Tae Ho Lee |
spellingShingle |
Nami Kim Dongmei Chen Xiao Zhen Zhou Tae Ho Lee Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease International Journal of Molecular Sciences death-associated protein kinase 1 (DAPK1) Alzheimer’s disease (AD) ischemic stroke neuronal cell death phosphorylation |
author_facet |
Nami Kim Dongmei Chen Xiao Zhen Zhou Tae Ho Lee |
author_sort |
Nami Kim |
title |
Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease |
title_short |
Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease |
title_full |
Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease |
title_fullStr |
Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease |
title_full_unstemmed |
Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease |
title_sort |
death-associated protein kinase 1 phosphorylation in neuronal cell death and neurodegenerative disease |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-06-01 |
description |
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 (Ca<sup>2+</sup>/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. |
topic |
death-associated protein kinase 1 (DAPK1) Alzheimer’s disease (AD) ischemic stroke neuronal cell death phosphorylation |
url |
https://www.mdpi.com/1422-0067/20/13/3131 |
work_keys_str_mv |
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