Caspase-3, Caspase-8, and Caspase-9 (CASP3/8/9)

Caspase-3, Caspase-8, and Caspase-9 are key members of the cysteine-aspartic acid protease family that serve as central regulators of programmed cell death, or apoptosis [1.2.1, 1.3.1]. Caspase-8 and Caspase-9 function as initiator caspases, triggered by extrinsic death receptor signals and intrinsic mitochondrial stress, respectively [1.1.2, 1.2.2]. These initiators then proteolytically activate Caspase-3, the primary executioner caspase responsible for the systematic dismantling of the cell by cleaving vital structural and regulatory proteins [1.1.3, 1.4.1]. Beyond apoptosis, these enzymes play roles in inflammation, cell differentiation, and tissue homeostasis [1.2.3, 1.3.2]. In diseases such as cancer, these caspases are often downregulated or inhibited to allow for uncontrolled cell survival, making their reactivation a therapeutic goal [1.2.4, 1.2.5]. Conversely, in neurodegenerative conditions and traumatic brain injury, excessive caspase activity leads to pathological cell loss, prompting the development of caspase inhibitors like Emricasan to preserve tissue function [1.2.1, 1.4.3]. Therapeutic modulation of these targets requires careful balance to avoid systemic toxicity or the potential promotion of tumorigenesis [1.2.2, 1.3.2].

Other names

Cysteine-aspartic acid protease 3Cysteine-aspartic acid protease 8Cysteine-aspartic acid protease 9Apoptotic caspasesCASP3CASP8CASP9CPP32FLICEMCH6ApopainMACHICE-LAP6

Direct inhibition of the catalytic cysteine residue within the active site of the caspase, preventing the proteolytic cleavage of downstream substrates and halting the apoptotic cascade [1.2.1, 1.2.2].