The NLRP3 inflammasome is a three-part complex: NLRP3 (the sensor), ASC (the adaptor), and caspase-1 (the effector). When activated by danger signals such as ATP, uric acid crystals, amyloid-beta, or silica, NLRP3 undergoes a conformational change. It recruits ASC proteins, which form a speck—a large signaling platform. This platform then cleaves caspase-1, which in turn cleaves the precursor cytokines pro-IL-1β and pro-IL-18 into their active, pro-inflammatory forms. Caspase-1 also cleaves gasdermin D, causing a highly inflammatory form of cell death called pyroptosis.
Gout is caused by MSU crystal deposition in joints, leading to agonizing pain and swelling. MSU crystals are a classic NLRP3 activator. VENX-201