Caspase-1, Caspase-4, Caspase-8, Caspase-9, and Caspase-10 (CASP1, CASP4, CASP8, CASP9, CASP10)

Caspases (cysteine-aspartic proteases) are a family of protease enzymes that play essential roles in programmed cell death and inflammation. This specific group encompasses inflammatory caspases (Caspase-1 and -4) and initiator caspases (Caspase-8, -9, and -10). Caspase-1 and -4 are key components of the inflammasome, responsible for processing pro-inflammatory cytokines like IL-1β and IL-18 and initiating pyroptosis [UniProt: P29466, P49662]. Caspase-8, -9, and -10 act as initiators in the apoptotic signaling pathways, where they activate executioner caspases in response to death receptor ligation or mitochondrial stress [UniProt: Q14790, P55211]. Dysregulation of these enzymes is implicated in a wide range of diseases, including chronic inflammatory conditions, neurodegenerative disorders, and various cancers. Therapeutic development focuses on small-molecule inhibitors, such as emricasan and belnacasan, which aim to modulate these pathways to treat conditions like non-alcoholic steatohepatitis (NASH) or inflammatory diseases [DrugBank: DB12009, PubMed: 30103115].

Other names

Cysteine-aspartic acid proteasesCysteine-dependent aspartate-directed proteasesICE-like proteasesCaspase-like cysteine proteasesCaspase family

Covalent or non-covalent inhibition of the catalytic cysteine residue within the active site, blocking the processing of pro-inflammatory cytokines or the activation of the apoptotic protease cascade [PubMed: 28234320].