Calpain research for drug discovery: challenges and potential

被引：213

作者：

Ono, Yasuko ^{[1
]}

Saido, Takaomi C. ^{[2
]}

Sorimachi, Hiroyuki ^{[1
]}

机构：

[1] Tokyo Metropolitan Inst Med Sci IGAKUKEN, Calpain Project, Dept Adv Sci Biomol, Setagaya Ku, 2-1-6 Kamikitazawa, Tokyo 1568506, Japan

[2] RIKEN Brain Sci Inst, Lab Proteolyt Neurosci, 2-1 Hirosawa, Wako, Saitama 3510198, Japan

来源：

NATURE REVIEWS DRUG DISCOVERY | 2016年 / 15卷 / 12期

基金：

日本学术振兴会;

关键词：

CALCIUM-DEPENDENT PROTEASE; MUSCLE-SPECIFIC CALPAIN; ACTIVATED NEUTRAL PROTEASE; PHOTORECEPTOR CELL-DEATH; PLURIPOTENT STEM-CELLS; SMALL-SUBUNIT GENE; DYSTROPHY TYPE 2A; MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; MOUSE MODEL;

D O I：

10.1038/nrd.2016.212

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Calpains are a family of proteases that were scientifically recognized earlier than proteasomes and caspases, but remain enigmatic. However, they are known to participate in a multitude of physiological and pathological processes, performing 'limited proteolysis' whereby they do not destroy but rather modulate the functions of their substrates. Calpains are therefore referred to as 'modulator proteases'. Multidisciplinary research on calpains has begun to elucidate their involvement in pathophysiological mechanisms. Therapeutic strategies targeting malfunctions of calpains have been developed, driven primarily by improvements in the specificity and bioavailability of calpain inhibitors. Here, we review the calpain superfamily and calpain-related disorders, and discuss emerging calpain-targeted therapeutic strategies.

引用

页码：854 / 876

页数：23

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