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

2019 ◽  
Vol 20 (13) ◽  
pp. 3131 ◽  
Author(s):  
Nami Kim ◽  
Dongmei Chen ◽  
Xiao Zhen Zhou ◽  
Tae Ho Lee
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Biological Processes ◽  
Death Associated Protein Kinase ◽  
The Brain

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.

scholarly journals Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases

2018 ◽  
Vol 19 (10) ◽  
pp. 3082 ◽  
Author(s):  
Hao Chi ◽  
Hui-Yun Chang ◽  
Tzu-Kang Sang
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Alpha Synuclein ◽  
Adult Brain ◽  
Pathological Feature ◽  
The Central Nervous System ◽  
Cell Death Mechanisms ◽  
The Brain

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In normal physiological conditions, neuronal cell death is restricted in the adult brain, even in aged individuals. However, in the pathological conditions of various neurodegenerative diseases, cell death and shrinkage in a specific region of the brain represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe evidence for cell death in the context of individual common neurodegenerative diseases, discussing our current understanding of cell death by connecting with renowned pathogenic proteins, including Tau, amyloid-beta, alpha-synuclein, huntingtin and TDP-43.

scholarly journals Calcium/Calmodulin–Dependent Protein Kinase II in Cerebrovascular Diseases

2021 ◽  
Author(s):  
Xuejing Zhang ◽  
Jaclyn Connelly ◽  
Edwin S. Levitan ◽  
Dandan Sun ◽  
Jane Q. Wang
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cerebrovascular Diseases ◽  
Biological Processes ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein ◽  
The Brain

AbstractCerebrovascular disease is the most common life-threatening and debilitating condition that often leads to stroke. The multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key Ca2+ sensor and an important signaling protein in a variety of biological systems within the brain, heart, and vasculature. In the brain, past stroke-related studies have been mainly focused on the role of CaMKII in ischemic stroke in neurons and established CaMKII as a major mediator of neuronal cell death induced by glutamate excitotoxicity and oxidative stress following ischemic stroke. However, with growing understanding of the importance of neurovascular interactions in cerebrovascular diseases, there are clearly gaps in our understanding of how CaMKII functions in the complex neurovascular biological processes and its contributions to cerebrovascular diseases. Additionally, emerging evidence demonstrates novel regulatory mechanisms of CaMKII and potential roles of the less-studied CaMKII isoforms in the ischemic brain, which has sparked renewed interests in this dynamic kinase family. This review discusses past findings and emerging evidence on CaMKII in several major cerebrovascular dysfunctions including ischemic stroke, hemorrhagic stroke, and vascular dementia, focusing on the unique roles played by CaMKII in the underlying biological processes of neuronal cell death, neuroinflammation, and endothelial barrier dysfunction triggered by stroke. We also highlight exciting new findings, promising therapeutic agents, and future perspectives for CaMKII in cerebrovascular systems.

scholarly journals Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hui-Min Yap ◽  
Kwan-Liang Lye ◽  
Loh Teng-Hern Tan
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Monosodium Glutamate ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Glutamate Toxicity ◽  
Extracellular Glutamate

The increased concentration of extracellular glutamate has been reported to play a key role in most of the neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, even though its importance as an amino acid neurotransmitter in mammalian. Glutamate toxicity, which can be caused by excessive intake of monosodium glutamate (MSG), is the major contributor to pathological neuronal cell death. It causes neuronal dysfunction and degeneration in the central nervous system (CNS). Glutamate neurotoxicity can be categorized into two forms, which are receptor-mediated glutamate excitotoxicity and non-receptor mediated glutamate oxidative toxicity. The receptor-mediated glutamate excitotoxicity involved excessive stimulation of glutamate receptors (GluRs) which lead to excessive ion calcium (Ca2+) influx and activates a cell death cascade involving the accumulation of mitochondrially generated reactive oxygen species (ROS). Studies showed excessive extracellular glutamate leads to nerve cell death via the activation of N-methyl-Daspartate (NMDA) receptors in the cases of trauma or stroke. Whereas non-receptor mediated oxidative toxicity involved the breakdown of the cystine/glutamate antiporter (xc - ) mechanism, which leads to the depletion of glutathione (GSH) and causes oxidative stress and cell death. The cystine/glutamate antiporter couples the import of cystine to the export of glutamate. The increased concentration of extracellular glutamate could inhibit the uptake of cystine, which is required for the synthesis of the intracellular antioxidant GSH. GSH plays an important role in the disposal of peroxides by brain cells and in the protection against ROS. Depletion of GSH renders the cell to oxidative stress and ultimately leading to cell death. This article aims to provide a comprehensive review of neurodegenerative diseases and the role of neurotoxin agents, glutamate in these diseases.

scholarly journals Death-associated protein kinase 1 phosphorylates NDRG2 and induces neuronal cell death

2016 ◽  
Vol 24 (2) ◽  
pp. 238-250 ◽  
Author(s):  
Mi-Hyeon You ◽  
Byeong Mo Kim ◽  
Chun-Hau Chen ◽  
Michael J Begley ◽  
Lewis C Cantley ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Death Associated Protein Kinase
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