Caspase-3 and Caspase-9 (CASP3 and CASP9)

Caspase-3 and Caspase-9 are intracellular cysteine-aspartic proteases pivotal to apoptosis. Caspase-9 acts upstream as an initiator, activated by apoptosome formation after mitochondrial cytochrome c release; it then activates downstream effectors including Caspase-3. Caspase-3 is considered the major executioner, cleaving vital cellular substrates to dismantle the cell, defining the morphological changes of apoptosis[1][2][3][5][7]. Beyond apoptosis, both have non-apoptotic roles including regulation of differentiation, immune response, and mitochondrial homeostasis[2][3]. They are therapeutic targets in diverse diseases with disordered cell death, and agents modulating their activity are used or under investigation for cancer, neurodegenerative diseases, trauma, and immune pathologies[4][6][8]. Both proteins are regulated via zymogen activation, protein-protein interactions (e.g., with Apaf-1 and XIAP), and post-translational modifications[1][5][7]. Their activity is closely monitored as a biomarker in clinical and preclinical research, and they present both therapeutic opportunities and safety challenges depending on the disease context.

Other names

CPP32ApopainSCA-1ICE-LAP6Mch6Cysteine-aspartic protease

Inhibition of caspase protease activity blocks apoptosis; Chemical-induced dimerization for iCasp9 triggers apoptosis in gene therapy; Cancer and neurodegeneration drugs may *activate* or *inhibit* caspase-3/-9 to regulate apoptosis; Chemotherapy-mediated activation that leads to tumor cell death