Caspase-8 and effector caspases (CASP8/3/6/7)

Caspase-8 is a cysteine-aspartic protease that serves as the primary initiator of the extrinsic apoptosis pathway, activated upon the ligation of death receptors such as Fas and TNFR1. Once activated, Caspase-8 triggers a proteolytic cascade by cleaving and activating the effector caspases, specifically Caspase-3, Caspase-6, and Caspase-7, which execute the final stages of programmed cell death by dismantling key cellular structures. Beyond its pro-apoptotic role, Caspase-8 is a critical regulator of cell survival, as it actively inhibits necroptosis by cleaving the kinases RIPK1 and RIPK3. In oncology, these caspases are often downregulated or inhibited by cancer cells to evade apoptosis, making their reactivation through death receptor agonists or SMAC mimetics a key therapeutic strategy. Conversely, in neurodegenerative and inflammatory diseases, excessive caspase activity leads to pathological cell loss, suggesting that selective caspase inhibition could provide therapeutic benefits.

Other names

Caspase-8 (CASP8)Caspase-3 (CASP3)Caspase-6 (CASP6)Caspase-7 (CASP7)Apoptotic caspasesExecutioner caspasesInitiator caspase-8MACH (MORT1-associated CED-3 homolog)FLICE (FADD-like ICE)Mch5CPP32 (Caspase-3)Yama (Caspase-3)Apopain (Caspase-3)Mch2 (Caspase-6)Mch3 (Caspase-7)

Activation of Caspase-8 via death receptor agonism to induce apoptosis in malignant cells; Inhibition of Caspase-8 and effector caspases to prevent pathological cell death in inflammatory and neurodegenerative conditions.