Caspase-mediated apoptotic pathway

The Caspase-mediated apoptotic pathway is a highly regulated biological process essential for maintaining cellular homeostasis and eliminating damaged or redundant cells. It is primarily driven by a family of cysteine proteases known as caspases, which are activated through two main routes: the intrinsic (mitochondrial) pathway and the extrinsic (death receptor) pathway. The intrinsic pathway is triggered by internal stressors like DNA damage, leading to mitochondrial outer membrane permeabilization and the formation of the apoptosome, while the extrinsic pathway is initiated by the binding of extracellular ligands to death receptors such as Fas or TNFR1. Both pathways converge on the activation of executioner caspases, such as Caspase-3 and Caspase-7, which systematically dismantle the cell by cleaving structural and functional proteins. In many diseases, this pathway is dysregulated; for instance, cancer cells often evade apoptosis by overexpressing anti-apoptotic proteins like Bcl-2, whereas excessive caspase activation contributes to neuronal loss in neurodegenerative disorders. Consequently, the pathway is a major therapeutic target, with drugs like Venetoclax inhibiting Bcl-2 to induce apoptosis in leukemia, and various caspase inhibitors being investigated to treat inflammatory and ischemic conditions.

Other names

Caspase-dependent apoptosisCaspase cascadeApoptotic signaling pathwayProgrammed cell death pathwayCaspase-mediated cell death

Inhibition of anti-apoptotic Bcl-2 family proteins, direct inhibition of caspase enzymatic activity, activation of pro-apoptotic death receptors, and inhibition of Inhibitor of Apoptosis Proteins (IAPs) using Smac mimetics.