NLR family pyrin domain containing 3 inflammasome complex (NLRP3 inflammasome) (NLRP3 inflammasome)

The NLRP3 inflammasome is a high-molecular-weight multiprotein complex located in the cytosol of various cells, most notably professional antigen-presenting cells like macrophages and dendritic cells (UniProt KB - Q96P20). It functions as a key sensor of the innate immune system, responding to a diverse range of stimuli including microbial motifs, endogenous danger signals such as ATP or uric acid crystals, and environmental irritants (PubMed: 24854589). The complex consists of the NLRP3 sensor, the ASC adapter protein, and the effector enzyme pro-caspase-1. Activation of the complex triggers the proteolytic cleavage of pro-caspase-1 into its active form, which then processes the precursors of interleukin-1β (IL-1β) and interleukin-18 (IL-18) into their mature, secreted forms, while also inducing a form of programmed cell death known as pyroptosis (PubMed: 31034466). Chronic or excessive activation of the NLRP3 inflammasome is a central driver in the pathogenesis of numerous inflammatory, metabolic, and neurodegenerative diseases (PubMed: 27950320). As a result, it is a highly sought-after therapeutic target, with various small molecules in clinical development aimed at inhibiting its activation to mitigate systemic and local inflammation (PubMed: 29305584).

Other names

Cryopyrin inflammasomeNALP3 inflammasomePYPAF1 inflammasomeCIAS1 inflammasomeCaspase-1-activating complex

Direct binding to the NLRP3 NACHT domain to inhibit its ATPase activity, thereby preventing the oligomerization of NLRP3 and the subsequent recruitment of ASC and pro-caspase-1, which blocks the maturation of pro-inflammatory cytokines.