NOD-like receptor protein 3 (NLRP3)

NOD-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor predominantly expressed in macrophages. It serves as a sensor for pathogen-associated molecular patterns and danger signals from damaged cells. Upon activation by diverse stimuli—including extracellular ATP, crystalline uric acid, or microbial components—NLRP3 oligomerizes with the adaptor ASC and pro-caspase‑1 to form the NLRP3 inflammasome complex. This leads to autocatalytic activation of caspase‑1, which processes pro-inflammatory cytokines interleukin‑1β and interleukin‑18 into their active forms for secretion. Caspase‑1 also cleaves gasdermin D, triggering pyroptotic cell death. The NLRP3 inflammasome plays a central role in host defense but is also implicated in numerous inflammatory diseases when dysregulated. Pharmacological inhibitors such as MCC950 and dapansutrile are under investigation for treating conditions driven by aberrant NLRP3 activity.

Other names

NACHT, LRR and PYD domains-containing protein 3CryopyrinCIAS1PYPAF1

Direct inhibition of NLRP3 oligomerization/activation by small molecules such as MCC950 and dapansutrile, preventing assembly of the inflammasome complex and subsequent activation of caspase‑1 and release of pro-inflammatory cytokines