Microglial cathepsin B as a key driver of inflammatory brain diseases and brain aging

被引：90

作者：

Nakanishi, Hiroshi ^{[1
]}

机构：

[1] Yasuda Womens Univ, Fac Pharm, Dept Pharmacol, Hiroshima, Japan

来源：

NEURAL REGENERATION RESEARCH | 2020年 / 15卷 / 01期

关键词：

brain aging; caspase-1; cathepsin B; inflammatory brain diseases; interleukin-1; beta; microglia; mitochondrial transcription factor A; neuroinflammation; nuclear factor-kappa B; oxidative stress; MEMORY; SECRETION; ROLES; MODEL;

D O I：

10.4103/1673-5374.264444

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Interleukin-1 beta is a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer's disease, Parkinson's disease, stroke and persistent pain. Activated microglia are the main cellular source of interleukin-1 beta in the brain. Cathepsin B is associated with the production and secretion of interleukin-1 beta through pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes. The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A, which can stabilize mitochondrial DNA. Therefore, microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging. Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging.

引用

页码：25 / 29

页数：5

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