Caspase-1 and Caspase-3 (CASP1; CASP3)

Caspase-1 and caspase-3 are essential members of the cysteine-aspartic acid protease (caspase) family, playing distinct yet interconnected roles in cellular signaling and death [1, 6]. Caspase-1, historically known as interleukin-1 beta converting enzyme (ICE), is the primary inflammatory caspase responsible for the proteolytic maturation of pro-inflammatory cytokines such as IL-1β and IL-18, as well as the induction of pyroptosis [2, 7, 9]. Caspase-3 is a central executioner caspase in the apoptotic pathway, responsible for cleaving structural and regulatory proteins to orchestrate cell dismantling [3, 4, 15]. Both enzymes are significant therapeutic targets; caspase-1 is targeted with inhibitors like belnacasan to treat autoinflammatory and neuroinflammatory diseases [2, 21]. Caspase-3 is modulated through activation (e.g., with PAC-1) to induce apoptosis in cancer cells or through inhibition to prevent pathological cell loss in stroke and neurodegeneration [5, 8]. The activation of caspase-1 can also lead to the activation of caspase-3 in certain contexts, such as the AIM2 inflammasome response [14]. Despite their therapeutic potential, targeting these caspases presents challenges due to their fundamental roles in maintaining tissue homeostasis and normal developmental processes [1, 10]. High selectivity is required to avoid systemic toxicity, immunosuppression, or unintended cell survival [12, 16]. Biomarkers such as cleaved caspase-3 and caspase-cleaved cytokeratin-18 are used to monitor the efficacy of treatments targeting these pathways [13, 18]. Overall, these enzymes represent a critical junction between inflammation and cell death, making them pivotal in the study of diverse pathologies [6, 12].

Other names

Interleukin-1 beta-converting enzymeICEApopainCPP32SCA-1YamaCASP1CASP3

Inhibition of pro-inflammatory cytokine maturation (Caspase-1); Inhibition or activation of apoptotic execution (Caspase-3)