Caspase (Cysteine-aspartic protease) (CASP)

Caspases are a family of cysteine-aspartic proteases that act as the central executioners of programmed cell death, or apoptosis, and also play critical roles in inflammation and cell differentiation [1, 4]. They are synthesized as inactive zymogens (pro-caspases) and are activated through proteolytic cleavage in response to internal or external death signals, such as DNA damage or death receptor ligation [2, 4]. The pathway is divided into initiator caspases (e.g., Caspase-8, Caspase-9) and executioner caspases (e.g., Caspase-3, Caspase-7), which collectively dismantle the cell by cleaving hundreds of specific substrates [1, 2]. In oncology, many tumors develop mechanisms to evade apoptotic caspase signaling, leading to chemoresistance and uncontrolled growth, making the reactivation of these enzymes a key therapeutic goal [2, 4]. Conversely, excessive caspase activity is linked to the pathological cell loss seen in neurodegenerative diseases, stroke, and chronic liver conditions [3, 4]. Drugs like Emricasan have been developed to inhibit these enzymes to treat liver fibrosis, while others like Belnacasan target inflammatory caspases to treat autoimmune disorders [3]. However, therapeutic development is complicated by the need for high specificity to avoid disrupting essential physiological processes and potential systemic toxicity [3, 4].

Other names

Cysteine-aspartic proteaseCysteine-dependent aspartate-directed proteaseICE-like proteaseApoptotic protease

Caspase inhibition to prevent pathological cell death or Caspase activation to induce apoptosis in malignant cells.