Inflammasome complex

Inflammasome complexes are high-molecular-weight multimeric protein platforms that form in the cytosol of cells, primarily myeloid cells, in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) (PMID: 11812993). These complexes typically consist of a sensor protein (such as NLRP3, NLRC4, or AIM2), an adapter protein (ASC), and an effector protease (pro-caspase-1) (UniProt: Q96P20). Upon activation, the inflammasome triggers the proteolytic cleavage of pro-caspase-1 into active caspase-1, which subsequently processes the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) into their mature, secreted forms (PMID: 30770915). Additionally, inflammasome activation can lead to pyroptosis, a form of programmed inflammatory cell death mediated by gasdermin D. Dysregulation of inflammasome activity is linked to a wide range of chronic inflammatory and autoimmune conditions, including cryopyrin-associated periodic syndromes (CAPS), gout, type 2 diabetes, and Alzheimer's disease (StatPearls: NBK537027). Consequently, the inflammasome, particularly the NLRP3 variant, has emerged as a major therapeutic target for small-molecule inhibitors and biologics aimed at modulating excessive inflammation.

Other names

InflammasomeNLR-containing complexPyroptosomeCaspase-1 activating complex

Inhibition of inflammasome assembly by targeting sensor proteins (e.g., NLRP3) to prevent oligomerization, or direct inhibition of the effector enzyme caspase-1, thereby preventing the maturation of IL-1β and IL-18 (PMID: 31534224).