Pro-apoptotic enzymes (Caspases)

Pro-apoptotic enzymes, primarily represented by the caspase family of cysteine-aspartic proteases, are the central executioners of programmed cell death (apoptosis) [1,2]. These enzymes are synthesized as inactive zymogens (pro-caspases) and are activated through proteolytic cleavage in response to intrinsic mitochondrial stress or extrinsic death receptor signaling [2,3]. Once activated, initiator caspases (such as Caspase-8 and Caspase-9) activate executioner caspases (such as Caspase-3 and Caspase-7), which systematically dismantle the cell by cleaving structural proteins and DNA repair enzymes [3]. In oncology, many therapies aim to reactivate these enzymes to overcome the apoptosis resistance that characterizes malignant cells [4]. Conversely, the pathological activation of pro-apoptotic enzymes is a hallmark of neurodegenerative diseases, stroke, and myocardial infarction, where excessive cell death leads to functional decline [5]. Consequently, both caspase activators (for cancer) and caspase inhibitors (for degenerative and inflammatory conditions) have been developed as therapeutic candidates [6,7]. Beyond their role in cell death, certain pro-apoptotic enzymes like Caspase-1 are also involved in the maturation of inflammatory cytokines, linking apoptosis to the innate immune response [2]. Sources: [1] https://www.uniprot.org/keywords/KW-0053 [2] https://pubmed.ncbi.nlm.nih.gov/26348386/ [3] https://pubmed.ncbi.nlm.nih.gov/10848513/ [4] https://pubmed.ncbi.nlm.nih.gov/26241031/ [5] https://pubmed.ncbi.nlm.nih.gov/11074189/ [6] https://pubchem.ncbi.nlm.nih.gov/compound/Emricasan [7] https://pubchem.ncbi.nlm.nih.gov/compound/Belnacasan

Other names

CaspasesApoptotic proteasesCysteine-aspartic proteasesDeath proteasesCysteine-dependent aspartate-directed proteases

Direct inhibition of the catalytic site of caspase enzymes to prevent programmed cell death or the maturation of pro-inflammatory cytokines; or activation of zymogens to induce apoptosis in target cells.