棕榈酰化
炎症体
二硫仑
药理学
上睑下垂
NLRC4型
半胱氨酸蛋白酶1
化学
目标2
药品
医学
炎症
生物化学
免疫学
酶
半胱氨酸
作者
Jie Xu,Joseph M. Pickard,Gabriel Núñez
出处
期刊:Cell Reports
[Cell Press]
日期:2024-08-01
卷期号:43 (8): 114609-114609
被引量:37
标识
DOI:10.1016/j.celrep.2024.114609
摘要
The NLRP3 inflammasome is dysregulated in autoinflammatory disorders caused by inherited mutations and contributes to the pathogenesis of several chronic inflammatory diseases. In this study, we discovered that disulfiram, a safe US Food and Drug Administration (FDA)-approved drug, specifically inhibits the NLRP3 inflammasome but not the NLRC4 or AIM2 inflammasomes. Disulfiram suppresses caspase-1 activation, ASC speck formation, and pyroptosis induced by several stimuli that activate NLRP3. Mechanistically, NLRP3 is palmitoylated at cysteine 126, a modification required for its localization to the trans-Golgi network and inflammasome activation, which was inhibited by disulfiram. Administration of disulfiram to animals inhibited the NLRP3, but not NLRC4, inflammasome in vivo. Our study uncovers a mechanism by which disulfiram targets NLRP3 and provides a rationale for using a safe FDA-approved drug for the treatment of NLRP3-associated inflammatory diseases.
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