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Review

Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease

1
Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
2
Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
3
Division of Translational Therapeutics, Department of Medicine and Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3131; https://doi.org/10.3390/ijms20133131
Received: 17 June 2019 / Accepted: 25 June 2019 / Published: 26 June 2019
(This article belongs to the Special Issue Kinase Signal Transduction 2019)
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. View Full-Text
Keywords: death-associated protein kinase 1 (DAPK1); Alzheimer’s disease (AD); ischemic stroke; neuronal cell death; phosphorylation death-associated protein kinase 1 (DAPK1); Alzheimer’s disease (AD); ischemic stroke; neuronal cell death; phosphorylation
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MDPI and ACS Style

Kim, N.; Chen, D.; Zhou, X.Z.; Lee, T.H. Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease. Int. J. Mol. Sci. 2019, 20, 3131. https://doi.org/10.3390/ijms20133131

AMA Style

Kim N, Chen D, Zhou XZ, Lee TH. Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease. International Journal of Molecular Sciences. 2019; 20(13):3131. https://doi.org/10.3390/ijms20133131

Chicago/Turabian Style

Kim, Nami, Dongmei Chen, Xiao Z. Zhou, and Tae H. Lee 2019. "Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease" International Journal of Molecular Sciences 20, no. 13: 3131. https://doi.org/10.3390/ijms20133131

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