作者
Michael JD Daniels, Jack Rivers-Auty, Tom Schilling, Nicholas G Spencer, William Watremez, Victoria Fasolino, Sophie J Booth, Claire S White, Alex G Baldwin, Sally Freeman, Raymond Wong, Clare Latta, Shi Yu, Joshua Jackson, Nicolas Fischer, Violette Koziel, Thierry Pillot, James Bagnall, Stuart M Allan, Pawel Paszek, James Galea, Michael K Harte, Claudia Eder, Catherine B Lawrence, David Brough
发表日期
2016/8/11
期刊
Nature communications
卷号
7
期号
1
页码范围
12504
出版商
Nature Publishing Group UK
简介
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of the proinflammatory cytokine interleukin-1β and is implicated in many inflammatory diseases. Here we show that several clinically approved and widely used NSAIDs of the fenamate class are effective and selective inhibitors of the NLRP3 inflammasome via inhibition of the volume-regulated anion channel in macrophages, independently of COX enzymes. Flufenamic acid and mefenamic acid are efficacious in NLRP3-dependent rodent models of inflammation in air pouch and peritoneum. We also show therapeutic effects of fenamates using a model of amyloid beta induced memory loss and a transgenic mouse model of Alzheimer’s disease. These data suggest that fenamate NSAIDs could be repurposed as NLRP3 …
学术搜索中的文章
MJD Daniels, J Rivers-Auty, T Schilling, NG Spencer… - Nature communications, 2016