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Compartmentalized necroptosis activation in excitotoxicityinduced axonal degeneration: a novel mechanism implicated in neurodegenerative disease pathology

查看全文 作　　者：Macarena S. [1]Arrazola;Felipe A. [2]Court 高影响力作者 机构地区：[1]Center for Integrative Biology, Faculty of Sciences, Universidad Mayor de Chile, Santiago, Cnile,FONDAP Center for Geroscience, Brain Health and Metabolism, Santiago, Chile;[2]Buck Institute for Research on Ageing, Novato, San Francisco, CA, USA高影响力机构 出　　处：《Neural Regeneration Research》索引2019年第14卷第8期,共2页高影响力期刊 基　　金：funded by grants from Geroscience Center for Brain Health and Metabolism(FONDAP-15150012,to FC);Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT,1150766,to FC);Comisión Nacional de Investigación Científica y Tecnológica,Fondecyt de Postdoctorado Project(3180313,to MA) 摘　　要：Excitotoxicity and neuronal cell death: Glutamate is the main excitatory neurotransmitter of the central nervous system and functionally involved in most brain activities, including brain development, synaptic plasticity, learning and memory. Exc让atory synaptic transmission is primarily mediated by ligana-gated ion channels, including a-amino-3-hydroxy-5-methylisoxazoIe-4-propionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. Activation of glutamate receptors, particularly NMDA receptors, usually leads to calcium influx, whicn can act as a second messenger for several processes to mediate synaptic activity and brain function. Nevertheless, excessive release of glutamate neurotransmitter may produce intracellular calcium overload, leading to a cascade of events mediating cytoskeleton damage accompanied w让h reactive oxygen species (ROS) generation, mitochondrial dysfunction and ultimately neuronal cell death. These toxic effects of glutamate are known as excitotoxicity. Neuronal excitotoxicity has been linked to several acute and chronic brain diseases, such as stroke/ischemia, epilepsy and a range of neurodegenerative disorders, including Alzheimer's disease (AD), Huntingtons disease, amyotrophic lateral sclerosis (ALS) and Parkinsons disease (PD), contributing to the neuronal lost in different brain regions. Unfortunately, treating nervous system disorders with general glutamate receptor blockers has been associated with undesirable side effects, becoming increasingly necessary to unravel downstream effectors in the excitotoxicity-dependent cell death pathway in order to develop novel therapeutic strategies. 关 键 词：Compartmentalized NECROPTOSIS ACTIVATION excitotoxicityinduced AXONAL NEURODEGENERATIVE DISEASE
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