Caspase-dependent apoptotic pathway

The caspase-dependent apoptotic pathway is a fundamental mechanism of programmed cell death characterized by the sequential activation of cysteine-aspartic proteases known as caspases (NIH, 2023). It is initiated through two main signaling routes: the extrinsic pathway, which involves death receptors like Fas and TNFR, and the intrinsic pathway, which is triggered by mitochondrial stress and the release of cytochrome c (StatPearls, 2023). These pathways converge on the activation of executioner caspases, primarily caspase-3, -6, and -7, which proteolytically cleave essential cellular proteins to execute cell death (PubMed, 2020). This pathway plays a critical role in maintaining tissue homeostasis and eliminating damaged or infected cells (NIH, 2023). Dysregulation of the pathway is linked to various diseases, including cancer, where cells evade apoptosis, and neurodegenerative disorders, where excessive cell death occurs (Frontiers, 2021). Therapeutic interventions often target specific components of this pathway, such as Bcl-2 inhibitors like venetoclax for leukemia or caspase inhibitors like emricasan for liver disease (NIH, 2021; PubMed, 2018). Monitoring the pathway's activity is typically achieved through biomarkers like cleaved caspase-3 and PARP fragments (PubMed, 2020). Challenges in targeting this pathway include achieving selectivity to avoid systemic toxicity and overcoming resistance mechanisms like the upregulation of inhibitor of apoptosis proteins (IAPs) (Frontiers, 2021).

Other names

Caspase-mediated apoptosisCaspase-dependent cell deathProteolytic apoptotic cascadeCaspase cascade

Activation of the caspase proteolytic cascade to induce apoptosis in cancer cells, or inhibition of caspases to prevent cell death in degenerative diseases.