Cysteine-aspartic protease family (Caspase family)

The Cysteine-aspartic protease family, commonly known as caspases, consists of enzymes that function as essential mediators of programmed cell death and inflammatory signaling. These proteases are organized into functional cascades where initiator caspases, such as Caspase-8 and Caspase-9, respond to apoptotic stimuli by activating executioner caspases like Caspase-3 and Caspase-7, which then dismantle the cell. A distinct subset of inflammatory caspases, including Caspase-1, regulates the maturation of proinflammatory cytokines during a specialized form of cell death known as pyroptosis. Dysregulation of these cascades is a hallmark of many pathologies; overactivity is linked to neurodegenerative disorders and tissue loss in ischemic injury, while evasion of caspase activation allows cancer cells to avoid apoptosis and proliferate uncontrollably. Therapeutic strategies include small-molecule inhibitors to prevent excessive cell death in inflammatory or degenerative diseases, as well as activators designed to restore apoptotic pathways in malignant cells. Additionally, inducible caspase systems are increasingly used as 'safety switches' in advanced cell therapies, such as CAR-T cells, to provide a mechanism for rapid cell elimination if severe toxicities occur.

Other names

Cysteine-dependent aspartate-directed proteasesCysteine-aspartic proteasesCED-3-like proteasesInterleukin-1 beta converting enzyme (ICE) familyApoptotic protease cascade

Caspase inhibitors typically act by binding to the catalytic cysteine residue in the active site to prevent substrate cleavage, thereby blocking apoptosis or cytokine maturation. Conversely, caspase activators or pro-caspase inducers promote the oligomerization and autolytic activation of zymogens to trigger cell death in target tissues like tumors.