caspase1mediated

Caspase-1-mediated refers to cellular processes governed by caspase-1, an inflammatory cysteine protease of the caspase family. Caspase-1 is produced as the inactive zymogen procaspase-1 and is activated upon assembly of inflammasomes, multiprotein complexes formed in response to pathogenic or danger signals.

Upon activation, caspase-1 cleaves proinflammatory cytokines pro-IL-1β and pro-IL-18 to their mature, active forms, IL-1β and IL-18, which are secreted and promote inflammatory responses. Additionally, caspase-1 cleaves gasdermin D (GSDMD) to release its N-terminal fragment, which oligomerizes to form pores in the cell membrane, leading to pyroptosis, a lytic form of programmed cell death that facilitates cytokine release.

Inflammasome activation and caspase-1 signaling contribute to host defense against infection but can drive pathology when dysregulated. Chronic or excessive caspase-1 activity is implicated in autoinflammatory diseases such as CAPS and in inflammatory conditions including gout, sepsis, and atherosclerosis.

Therapeutically, strategies include IL-1 blockers (e.g., anakinra, canakinumab) and efforts to inhibit caspase-1 or inflammasome components; research continues on specific inhibitors such as VX-765. The caspase-1–mediated pathway thus links cellular danger sensing to cytokine maturation and pyroptotic cell death, shaping inflammatory outcomes in health and disease.