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

• Published in: Neural regeneration research Vol. 15; no. 1; pp. 25 - 29
• Main Author: Nakanishi, Hiroshi
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.01.2020; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Department of Pharmacology, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima, Japan; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Aging; Aging (Biology); Alzheimer's disease; Autophagy; Binding sites; Brain; brain aging; caspase-1; cathepsin B; inflammatory brain diseases; interleukin-1β; microglia; mitochondrial transcription factor A; neuroinflammation; nuclear factor-κB; oxidative stress; Brain damage; Brain diseases; Care and treatment; Cathepsins; Development and progression; DNA; Health aspects; Hypoxia; Inflammation; Interleukins; Kinases; Microglia; Mitochondrial DNA; Nervous system diseases; Pain; Parkinson's disease; Proteins; Proteolysis; Review; Roles; Spinal cord; Stroke; Transcription (Genetics); Transcription factors; Tumor necrosis factor-TNF; United States; nuclear factor-κB; inflammatory brain diseases; neuroinflammation; cathepsin B; brain aging; mitochondrial transcription factor A; caspase-1; microglia; oxidative stress; interleukin-1β; Key Words: brain aging
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.264444

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.