中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 25-29.doi: 10.4103/1673-5374.264444

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

小胶质细胞组织蛋白酶B是炎性脑疾病和脑老化的关键驱动因素

  

  • 出版日期:2020-01-15 发布日期:2020-05-14

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

Hiroshi Nakanishi*   

  1. Department of Pharmacology, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima, Japan
  • Online:2020-01-15 Published:2020-05-14
  • Contact: Hiroshi Nakanishi, PhD,nakanishi-h@yasuda-u.ac.jp
  • Supported by:
    This project was founded by JSPS KAKENHI, No. 24390416, JP15H05015, 15K15684 and JP16H01304 (all to HN).

摘要: orcid: 0000-0001-5671-9696 (Hiroshi Nakanishi)

Abstract: 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. Cathepsin 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 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.

Key words: brain aging, caspase-1, cathepsin B, inflammatory brain diseases, interleukin-1β, microglia,  mitochondrial transcription factor A, neuroinflammation, nuclear factor-κB, oxidative stress