Caspase

Caspases are cysteine-dependent proteases that regulate apoptosis, inflammatory response, proliferation, differentiation, immune responses, and homeostasis^[1][2]. Mechanistically, apoptotic caspases activate through recruitment to signaling complexes, upstream activator caspases, or autoactivation, producing conserved amplifying cascades^[1]. In inflammasome biology, caspase-1 processes IL-1β and IL-18 and supports pyroptosis, linking innate immune sensing to inflammatory cell death^[3][4]. Disease models show pathway relevance: NLRP3-inflammasome-caspase-1 signaling is hyper-inducible in idiopathic pulmonary fibrosis, while apoptotic A549-cell co-culture increases caspase-1-dependent IL-1β production^[4]. Compared with related isoforms, caspase-6 differs from other executioner caspases because it mediates ZBP1-dependent inflammasome activation, PANoptosis, and host defense during influenza A virus infection^[5]. Caspase-7 also has a distinct inflammasome-linked role, because Nlrc4/Ipaf-dependent activation restricts Legionella pneumophila replication in macrophages^[6]. For experimental applications, caspase inhibitors help test caspase-mediated cell death, but clinical development faces inadequate efficacy, poor target specificity, and adverse side effects^[2]. Apaf-1 ligands further inhibit apoptosome-mediated procaspase-9 recruitment and reduce mitochondrial apoptosis phenotypes in cellular models^[7].