Cysteine-aspartic acid protease 3 (Caspase-3) (CASP3)

Caspase-3 is a pivotal member of the cysteine-aspartic acid protease family and serves as a primary executioner in the apoptotic cell death pathway [1, 14]. It is synthesized as an inactive 32 kDa zymogen (procaspase-3) that undergoes proteolytic cleavage by initiator caspases, such as Caspase-8 or Caspase-9, to form the active enzyme in response to internal or external death signals [1, 4, 11]. Once activated, Caspase-3 orchestrates the orderly dismantling of cellular components by cleaving a wide array of essential substrates, including poly(ADP-ribose) polymerase (PARP) and DNA repair enzymes [1, 14, 18]. In oncology, it is a significant therapeutic target for pro-apoptotic agents like PAC-1, which aim to selectively induce death in malignant cells that have evaded programmed cell death [3, 5, 13]. Conversely, the inhibition of Caspase-3 is a major clinical focus for neurodegenerative conditions—such as Alzheimer's, Parkinson's, and Huntington's diseases—and ischemic injuries like stroke, where its excessive activation leads to pathological cell loss [9, 10, 12, 16, 20]. Beyond its role in death, Caspase-3 also participates in non-apoptotic processes including tissue differentiation, stem cell physiology, and immune regulation, necessitating high specificity in drug targeting to avoid systemic toxicity [2, 17, 18].

Other names

CPP32SCA-1ApopainYamaCaspase 3Procaspase-3CPP-32CASP-3Cysteine-aspartic acid protease 3

Drugs modulate Caspase-3 through either direct inhibition of its catalytic cysteine residue to prevent apoptotic cell death or direct activation of the proenzyme form (procaspase-3) to induce apoptosis in malignant cells [3, 10, 14].