NLRP3 and pyroptosis blockers for treating inflammatory diseases
Rebecca C. Coll, Kate Schroder, Pablo Pelegrı́n
Abstract
functions in concert with the NLR family, caspase activation and recruitment domain (CARD)containing 4 (NLRC4); (v) absent in melanoma 2 (AIM2); and (vi) Pyrin (PYD) These inflammasome sensor proteins recognize distinct perturbations of homeostasis and form oligomers able to recruit the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) into the Glossary Cryopyrin-associated periodic syndromes (CAPS): rare autoinflammatory disorders resulting from gain-of-function mutations in NLRP3 and characterized by periodic fevers, sterile urticaria, and joint inflammation. CAPS incorporate three overlapping disease entities: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem autoinflammatory syndrome (NOMID). Gasdermin D (GSDMD): pore-forming protein that induces pyroptosis downstream of inflammasome activation. Inflammasome: signaling complex that activates inflammatory caspases. Most inflammasomes are multiprotein assemblies that activate the caspase-1 protease. The so-called 'non-canonical inflammasome' is a protein-lipid assembly that activates the protease function of caspase-11 in mice and caspase-4 and caspase-5 in humans.