Caspase-dependent apoptotic machinery

The caspase-dependent apoptotic machinery is a complex, highly regulated network of proteins that executes programmed cell death, a process essential for embryonic development and adult tissue homeostasis [4, 6]. This machinery is centered around a cascade of cysteine-aspartic proteases called caspases, which are activated through either the extrinsic (death receptor) or intrinsic (mitochondrial) pathways [3, 9]. In the intrinsic pathway, mitochondrial outer membrane permeabilization leads to the release of cytochrome c, which triggers the formation of the apoptosome and the subsequent activation of initiator Caspase-9 [5, 7]. These initiators then activate executioner caspases, such as Caspase-3 and Caspase-7, which proteolytically dismantle the cell by cleaving essential structural and functional proteins [8, 12]. Dysregulation of this machinery is central to many diseases; cancer cells often evade death by overexpressing anti-apoptotic Bcl-2 family proteins or Inhibitor of Apoptosis Proteins (IAPs), while excessive caspase activity is linked to neurodegeneration and inflammatory disorders [1, 2]. Therapeutic interventions include Bcl-2 inhibitors like venetoclax to restore apoptotic sensitivity in malignancies and caspase inhibitors like emricasan to mitigate pathological cell loss [3, 11, 13].

Other names

Caspase cascadeProgrammed cell death pathwayApoptotic signaling pathwayApoptotic machineryCaspase-mediated apoptotic pathway

Modulation of the apoptotic threshold through inhibition of anti-apoptotic proteins (e.g., Bcl-2), activation of pro-apoptotic factors, or direct inhibition of caspase proteolytic activity [1, 3].