Microglial cathepsin B as a key driver of inflammatory brain diseases and brain aging
Hiroshi Nakanishi
摘要：Interleukin-1β 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-1β in the brain. Cathep-sin B is associated with the production and secretion of interleukin-1β 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 degrada-tion 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 phar-maceutical interventions against inflammatory brain diseases and brain aging.
机标关键词：
资助基金：This project was founded by JSPS KAKENHI, (No. 24390416, JP15H05015, 15K15684 and JP16H0130)
论文发表日期：2020-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：5( 25-29 )
英文信息