Caspase apoptotic cascade

The caspase apoptotic cascade is a highly regulated sequence of proteolytic events mediated by a family of cysteine-aspartic proteases known as caspases (StatPearls, 2023). This cascade is the central executioner of programmed cell death (apoptosis) and can be triggered via the extrinsic pathway (death receptor-mediated) or the intrinsic pathway (mitochondria-mediated) (Nature Reviews Molecular Cell Biology, 2011). Initiator caspases, such as Caspase-8 and Caspase-9, are first activated and subsequently cleave and activate executioner caspases like Caspase-3, -6, and -7, which dismantle cellular components (PubMed, 2018). In many cancers, this cascade is suppressed, allowing for uncontrolled cell proliferation and survival, whereas in neurodegenerative and inflammatory diseases, it may be overactive (NIH, 2021). Therapeutic interventions aim to either reactivate the cascade in oncology using agents like BCL-2 inhibitors or IAP antagonists, or inhibit specific caspases to prevent pathological cell loss in conditions like liver cirrhosis or myocardial infarction (PubChem, 2024).

Other names

Apoptotic caspase cascadeCaspase-dependent apoptosis pathwayProgrammed cell death pathway

Direct inhibition of caspase proteolytic activity to prevent cell death, or indirect activation of the cascade via inhibition of anti-apoptotic proteins to induce apoptosis in cancer cells.