中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (3): 556-562.doi: 10.4103/1673-5374.228762

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

在神经元死亡过程中钙调蛋白调控所发挥的作用

  

  • 收稿日期:2017-12-26 出版日期:2018-03-15 发布日期:2018-03-15
  • 基金资助:

    国家自然科学基金,编号81571939&81772134;伍杰平国家卫生部医学基金,编号:320.6750.14118;湖南省自然科学基金,编号:2015JJ2187;中南大学教师研究基金会,编号:2014JSJJ 026

Regulatory role of calpain in neuronal death

Si-ying Cheng1, Shu-chao Wang2, Ming Lei1, Zhen Wang2, Kun Xiong2   

  1. 1 Xiangya Medical School, Central South University, Changsha, Hunan Province, China
    2 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
  • Received:2017-12-26 Online:2018-03-15 Published:2018-03-15
  • Contact: Kun Xiong, Ph.D.,xiongkun2001@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81571939 & 81772134; the Wu Jie-Ping Medical Foundation of the Minister of Health of China, No. 320.6750.14118; the Natural Science Foundation of Hunan Province of China, No.2015JJ2187; the Teacher Research Foundation of Central South University of China, No. 2014JSJJ026.

摘要:

钙蛋白酶是一类钙离子依赖性的蛋白酶,在病理条件下可由升高的细胞内钙离子过度活化。神经元调控性坏死、凋亡、自噬通路中的多种分子均可被钙蛋白酶降解,故钙蛋白酶在神经元死亡和神经系统疾病中发挥重要的作用。文章主要介绍了近年来钙蛋白酶在神经元死亡中调控机制中的研究及相关进展。程序性细胞死亡包括凋亡、自噬、调控性坏死,包括程序性坏死、凋亡、多聚ADP核糖聚合酶(PARP)和线粒体通透性转变(MPT)引起的调控性坏死,钙蛋白酶可通过降解程序性细胞死亡通路中的关键分子而调节、诱导各种细胞死亡途径。除了探索钙蛋白酶在程序性死亡的机制外,未来研究还需进一步探讨并寻找合适的钙蛋白酶抑制剂以达到抑制神经元死亡产生的神经保护作用的策略。

orcid:0000-0002-3103-6028(Kun Xiong)

关键词: 神经再生, 钙蛋白酶, 钙蛋白酶抑制蛋白, 中枢神经系统, 钙, 细胞凋亡, 自噬, B细胞淋巴瘤, 细胞周期蛋白依赖性激酶, 线粒体通透性转换

Abstract:

Calpains are a group of calcium-dependent proteases that are over activated by increased intracellular calcium levels under pathological conditions. A wide range of substrates that regulate necrotic, apoptotic and autophagic pathways are affected by calpain. Calpain plays a very important role in neuronal death and various neurological disorders. This review introduces recent research progress related to the regulatory mechanisms of calpain in neuronal death. Various neuronal programmed death pathways including apoptosis, autophagy and regulated necrosis can be divided into receptor interacting protein-dependent necroptosis, mitochondrial permeability transition-dependent necrosis, pyroptosis and poly (ADP-ribose)polymerase 1-mediated parthanatos. Calpains cleave series of key substrates that may lead to cell death or participate in cell death. Regarding the investigation of calpain-mediated programed cell death, it is necessary to identify specific inhibitors that inhibit calpain mediated neuronal death and nervous system diseases.

Key words: nerve regeneration, calpain, calpastatin, central nervous system, apoptosis, autophagy, B-cell lymphoma, cyclin-dependent kinases, mitochondrial permeability transition, neural regeneration