Caspase-1 (Interleukin-1 converting enzyme) (CASP1)

Caspase-1, also known as Interleukin-1 converting enzyme (ICE), is a cysteine protease that plays a pivotal role in the innate immune system by mediating the maturation of pro-inflammatory cytokines (UniProt P29466). It is the primary enzyme responsible for the proteolytic cleavage of inactive pro-interleukin-1 beta (pro-IL-1β) and pro-interleukin-18 (pro-IL-18) into their biologically active forms (PubMed: 15652446). This process typically occurs within the inflammasome, a multi-protein complex that assembles in response to various pathogen-associated or danger-associated molecular patterns (StatPearls: Inflammasome). Beyond cytokine processing, Caspase-1 induces pyroptosis, a highly inflammatory form of programmed cell death, through the cleavage of gasdermin D (PubMed: 26375003). Dysregulation of this pathway is a hallmark of numerous inflammatory conditions, including cryopyrin-associated periodic syndromes (CAPS), gout, and atherosclerosis (PubMed: 28192390). Pharmacological inhibition of Caspase-1, using small molecules like belnacasan (VX-765), aims to reduce the systemic burden of IL-1β and IL-18, offering a therapeutic approach for chronic inflammatory and neurodegenerative diseases (ClinicalTrials.gov: NCT00205465). While targeting this maturation process provides a potent anti-inflammatory effect, it also carries risks of immunosuppression and increased susceptibility to certain infections (PubMed: 24052492).

Other names

Interleukin-1 beta-converting enzymeICEIL1BCP45Caspase 1IL-1β maturation enzyme

Inhibition of the enzymatic activity of Caspase-1 to prevent the proteolytic cleavage of pro-interleukin-1 beta (pro-IL-1β) and pro-interleukin-18 (pro-IL-18) into their active, secreted forms (PubMed: 21742798).