Cysteine-aspartic proteases 3, 7, and 9 (CASP3, CASP7, CASP9) (CASP3, CASP7, CASP9)

Caspases 3, 7, and 9 are a group of cysteine-aspartic proteases that serve as the central executioners and initiators of the intrinsic (mitochondrial) apoptotic pathway [1, 14]. Caspase-9 is an initiator caspase that is activated upon the formation of the apoptosome complex following the release of cytochrome c from the mitochondria [6, 15]. Once active, Caspase-9 proteolytically cleaves and activates the executioner caspases, Caspase-3 and Caspase-7, which then dismantle the cell by cleaving a wide variety of structural and functional proteins [9, 16]. This cascade is a critical regulator of programmed cell death, and its dysregulation is implicated in numerous pathologies, including cancer, where evasion of apoptosis leads to tumor progression and chemoresistance [2, 7]. Conversely, excessive activation of these caspases is a primary driver of neuronal loss in neurodegenerative diseases like Alzheimer's and acute conditions such as stroke or traumatic brain injury [3, 19]. Therapeutic strategies targeting these enzymes include small-molecule inhibitors to prevent pathological cell death and IAP antagonists (SMAC mimetics) that relieve endogenous inhibition of these caspases to sensitize cancer cells to apoptosis [4, 10].

Other names

Caspase-3Caspase-7Caspase-9CPP32ApopainYamaMCH3MCH6ICE-LAP3ICE-LAP6APAF-3

Direct inhibition of the catalytic cysteine residue in the active site; Allosteric inhibition of enzyme activation; Relief of endogenous inhibition by IAPs (indirect).