Caspase-dependent apoptosis signaling

Caspase-dependent apoptosis signaling is a fundamental programmed cell death pathway characterized by the sequential activation of aspartate-specific cysteine proteases known as caspases. This signaling can be initiated through two primary routes: the extrinsic pathway, triggered by death receptor ligation (e.g., Fas, TNFR1), and the intrinsic pathway, which involves mitochondrial outer membrane permeabilization and the release of cytochrome c. Both pathways converge on the activation of executioner caspases, such as Caspase-3 and Caspase-7, which proteolytically degrade vital cellular components, leading to the morphological hallmarks of apoptosis. Dysregulation of this pathway is a hallmark of many diseases; for instance, its evasion is a key feature of cancer, while its overactivation contributes to neurodegeneration and tissue damage in ischemic conditions. Therapeutic strategies often aim to restore apoptosis in cancer cells using BH3 mimetics or death receptor agonists, or to inhibit it in degenerative diseases using caspase inhibitors. Monitoring the pathway often involves detecting biomarkers such as cleaved caspase-3 or cleaved PARP-1 in clinical samples.

Other names

Caspase-dependent apoptosis pathwayCaspase-mediated apoptosisCaspase cascadeIntrinsic and extrinsic apoptosis pathways

Induction or inhibition of the proteolytic cascade involving initiator and executioner caspases to regulate programmed cell death.