Mitochondrial Mechanisms of Neuronal Cell Death: Potential Therapeutics

被引：116
作者：
Dawson, Ted M. [1 ,2 ,3 ,4 ,6 ,7 ]
Dawson, Valina L. [1 ,2 ,3 ,4 ,5 ,7 ,8 ]
机构：
[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA
[6] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[7] Adrienne Helis Malvin Med Res Fdn, New Orleans, LA 70130 USA
[8] Diana Helis Henry Med Res Fdn, New Orleans, LA 70130 USA
来源：
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 57 | 2017年 / 57卷
关键词：
apoptosis; apoptosis-inducing factor; neurodegeneration; parthanatos; poly (ADP-ribose) polymerase; stroke; APOPTOSIS-INDUCING FACTOR; POLY(ADP-RIBOSE) POLYMERASE-1 ACTIVATION; PERMEABILITY TRANSITION PORE; NITRIC-OXIDE; GLUTAMATE NEUROTOXICITY; PARP INHIBITORS; ECONOMIC BURDEN; ATP SYNTHASE; DNA-DAMAGE; NMDA;
D O I：
10.1146/annurev-pharmtox-010716-105001
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Mitochondria lie at the crossroads of neuronal survival and cell death. They play important roles in cellular bioenergetics, control intracellular Ca2+ homeostasis, and participate in key metabolic pathways. Mutations in genes involved in mitochondrial quality control cause a myriad of neurodegenerative diseases. Mitochondria have evolved strategies to kill cells when they are not able to continue their vital functions. This review provides an overview of the role of mitochondria in neurologic disease and the cell death pathways that are mediated through mitochondria, including their role in accidental cell death, the regulated cell death pathways of apoptosis and parthanatos, and programmed cell death. It details the current state of parthanatic cell death and discusses potential therapeutic strategies targeting initiators and effectors of mitochondrial-mediated cell death in neurologic disorders.
引用
收藏
页码：437 / 454
页数：18
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