Apoptotic caspase cascade

The apoptotic caspase cascade is a fundamental biochemical pathway that executes programmed cell death in response to various physiological and pathological stimuli. It is characterized by the sequential activation of caspases, which are cysteine-aspartic proteases that exist as inactive pro-enzymes within the cytoplasm [1]. The cascade is typically initiated through either the extrinsic pathway, triggered by death receptors, or the intrinsic pathway, which involves mitochondrial outer membrane permeabilization and the release of cytochrome c [2][3]. Once initiated, initiator caspases like Caspase-8 or Caspase-9 activate executioner caspases, primarily Caspase-3, -6, and -7, which catalyze the cleavage of vital cellular proteins and lead to the characteristic morphological changes of apoptosis [1][3]. In clinical practice, this cascade is a major focus for drug development; pro-apoptotic drugs like Venetoclax aim to restore cascade activity in cancer cells, while caspase inhibitors like Emricasan have been investigated to prevent excessive cell death in liver disease and neurodegeneration [4][5]. However, targeting this pathway is complex due to the risk of systemic toxicity and the potential for unintended survival of damaged cells if the cascade is improperly inhibited [2].

Other names

Caspase activation cascadeProgrammed cell death pathwayCaspase-dependent apoptotic pathwayProteolytic apoptotic cascade

Modulation of the proteolytic activity of caspases or their upstream regulators to either induce or inhibit programmed cell death.