Caspase signaling cascade

The caspase signaling cascade refers to the hierarchical, enzyme-driven pathways involving the caspase family of cysteine-aspartic proteases that regulate programmed cell death (such as apoptosis), inflammation, and related processes[1][3][5]. Caspases are expressed as inactive zymogens and become activated in response to specific stimuli, functioning as initiator or effector enzymes in both the intrinsic (mitochondria-mediated) and extrinsic (death receptor-mediated) apoptotic pathways, as well as in inflammatory cascades[1][3]. Initiator caspases (e.g., caspase-2, -8, -9, -10) activate downstream executioner/effector caspases (e.g., caspase-3, -6, -7), which then cleave specific cellular substrates to orchestrate controlled cell dismantling, while inflammatory caspases (e.g., caspase-1, -4, -5) process pro-inflammatory cytokines[1][4]. Dysregulation of this cascade contributes to diverse diseases, and direct targeting of caspase activation—using inhibitors, RNA-based drugs, or small molecules—has become a major area of therapeutic development[2][3][4][5]. Important clarification: "Caspase signaling cascade" is a pathway or process, not a single molecule or receptor, and represents an aggregate of related proteases rather than a standalone druggable target. Precise drug targeting often focuses on individual caspase proteins (e.g., "Caspase-3", "Caspase-9") or specific complexes (e.g., apoptosome), rather than the cascade as a whole[1][2][4]. Thus, this entry is best used to guide more specific target selection.

Other names

Caspase pathwayCaspase cascadeApoptotic signaling cascadeCaspase-mediated pathway

Caspase inhibition (active site or substrate blocking), siRNA-mediated reduction of caspase synthesis, Small-molecule inhibition, Blockade of apoptosome or DISC assembly[3][4]