Caspase1dependent

Caspase-1-dependent refers to cellular processes that require the activity of caspase-1, a cysteine protease activated within multiprotein complexes called inflammasomes. In many immune cells, sensor proteins such as NLRP3, NLRC4, or AIM2 recruit the adaptor protein ASC and pro-caspase-1 to form the inflammasome. Proximity-induced autocatalytic cleavage then converts pro-caspase-1 into active caspase-1, which drives downstream inflammatory events.

A key function of caspase-1 is the proteolytic maturation of pro-inflammatory cytokines. It cleaves pro-IL-1β and pro-IL-18 into their active forms, IL-1β and IL-18, which are secreted to promote inflammation and recruit immune cells to sites of infection or injury. In parallel, caspase-1 cleaves gasdermin D (GSDMD), producing an N-terminal fragment that forms pores in the cell membrane. This pore formation can lead to a lytic form of cell death known as pyroptosis, and it facilitates rapid release of cytokines and danger signals.

Physiologically, caspase-1-dependent pathways contribute to host defense against pathogens and to the amplification of inflammatory responses during sterile injury. However, dysregulation or chronic activation of caspase-1 pathways is associated with autoinflammatory and metabolic diseases, including CAPS (cryopyrin-associated periodic syndromes), gout, atherosclerosis, and some forms of insulin resistance.

Clinically, strategies targeting caspase-1 activity or its downstream effectors, such as IL-1β, are used to treat inflammatory conditions. Caspase-1 inhibitors and IL-1 antagonists like anakinra and canakinumab illustrate this therapeutic approach. In summary, caspase-1-dependent processes integrate pathogen sensing with inflammatory execution, shaping both protective immunity and disease risk.