Caspase-3 (CASP3) (CASP3)

Caspase-3 is a cysteine-aspartic acid protease that serves as the primary executioner of the apoptotic pathway, playing a central role in the programmed death of cells [1, 7]. It is synthesized as an inactive zymogen, procaspase-3, which is activated through proteolytic cleavage by initiator caspases, such as Caspase-8 or Caspase-9, in response to internal or external cellular stress signals [2, 7]. Once activated, Caspase-3 cleaves a wide array of essential cellular substrates, including structural proteins and DNA repair enzymes like PARP, leading to the irreversible dismantling of the cell [1, 14]. Beyond its role in cell death, Caspase-3 is increasingly recognized for its involvement in non-apoptotic processes such as cell differentiation, tissue regeneration, and synaptic plasticity [3, 4, 8]. In the pharmaceutical industry, it is a major therapeutic target; activators like PAC-1 are being explored to induce apoptosis in cancer cells, while inhibitors are investigated to prevent pathological cell loss in neurodegenerative and cardiovascular diseases [6, 14, 21]. However, the target's involvement in vital homeostatic processes poses significant safety challenges, as systemic modulation could lead to developmental defects or promote tumor repopulation through sublethal signaling [24, 25].

Other names

CPP32SCA-1ApopainYamaCysteine-dependent aspartate-directed protease 3CASP-3Cysteine protease CPP32

Direct activation of procaspase-3 to induce apoptosis or competitive inhibition of the active site to prevent pathological cell death.