Caspasen

Caspases are a family of cysteine-aspartic proteases that regulate programmed cell death (apoptosis) and inflammatory processes. They are synthesized as inactive zymogens (procaspases) that require proteolytic cleavage to become active. Activation occurs in response to cellular stress and is mediated by multi-protein complexes such as the apoptosome and inflammasomes, or by adaptor proteins at death receptors.

Caspases are commonly categorized into initiator caspases (such as caspase-2, caspase-8, caspase-9, and caspase-10), executioner (effector) caspases (caspase-3, caspase-6, caspase-7), and inflammatory caspases (caspase-1, caspase-4, caspase-5; in mice, caspase-11 is often included). Initiators typically possess long prodomains with death effector or CARD motifs and activate downstream caspases by proteolytic cleavage. Executioners then activate by cleavage and dismantle the cell by targeting a broad range of substrates.

Mechanistically, caspases cleave after aspartate residues in substrate proteins. Executioner caspases trigger morphological and biochemical features of apoptosis, including DNA fragmentation, cell shrinkage, and membrane changes. Inflammatory caspases process pro-forms of cytokines such as interleukin-1β and interleukin-18 and can drive inflammatory cell death (pyroptosis) under certain conditions.

Dysregulation of caspases is associated with various diseases, including cancer, neurodegeneration, and autoimmune disorders. Caspases are thus targets of research and therapeutic development, with inhibitors and modulators used to study their roles in cell fate and inflammation.