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The NLRP3 inflammasome is a multi-protein complex responsible for the processing of the proinflammatory cytokine interleukin-1\u03b2 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\u2019s disease. These data suggest that fenamate NSAIDs could be repurposed as NLRP3 inflammasome inhibitors and Alzheimer\u2019s disease therapeutics.<\/jats:p>","DOI":"10.1038\/ncomms12504","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T06:43:31Z","timestamp":1470897811000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":426,"title":["Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer\u2019s disease in rodent models"],"prefix":"10.1038","volume":"7","author":[{"given":"Michael J. 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