Caspase-3, Caspase-7, and Caspase-9 (CASP3/7/9)

Caspase-3, Caspase-7, and Caspase-9 are essential cysteine-aspartic proteases that drive the intrinsic (mitochondrial) apoptotic pathway, a highly regulated process of programmed cell death [1, 7]. Caspase-9 acts as the initiator, becoming activated within the apoptosome complex after mitochondrial outer membrane permeabilization and the release of cytochrome c [2, 12]. Once active, Caspase-9 proteolytically processes and activates the executioner caspases, Caspase-3 and Caspase-7, which subsequently cleave a multitude of cellular substrates to execute the final stages of cell death, including DNA fragmentation and membrane blebbing [3, 5]. Dysregulation of this cascade is central to many pathologies: overactivation contributes to neuronal loss in neurodegenerative diseases like Alzheimer's and Parkinson's, as well as tissue damage in stroke and myocardial infarction [8, 10, 11]. Conversely, the evasion of caspase-mediated apoptosis is a hallmark of cancer, enabling tumor survival and resistance to therapy [3, 13]. Therapeutic strategies involve the use of caspase inhibitors, such as emricasan, to mitigate unwanted cell death in inflammatory or degenerative conditions, or the use of activators and indirect modulators like venetoclax to restore apoptotic pathways in cancer cells [4, 9, 13]. Monitoring the levels of cleaved Caspase-3 and other fragments serves as a vital biomarker for assessing the efficacy of these pro-apoptotic or anti-apoptotic treatments [11].

Other names

Apoptotic caspasesIntrinsic apoptotic caspasesCysteine-aspartic acid proteases 3, 7, and 9Executioner and initiator caspases

Caspase inhibition to prevent pathological cell death or Caspase activation to induce apoptosis in malignant cells.