Cysteine-aspartic proteases (Caspases) (Caspases)

Caspases are a family of cysteine proteases that serve as the primary mediators of programmed cell death, or apoptosis, and are also involved in inflammatory signaling (UniProt, 2023). They are typically classified into initiator caspases, which respond to death signals, and executioner caspases, which carry out the proteolysis of cellular components (PubMed, 2022). The apoptosis-autophagy pathway represents a complex regulatory network where autophagy can act as a survival mechanism or a precursor to cell death, often sharing molecular triggers with the caspase cascade (NCBI, 2022). In diseases like cancer, cells often develop mechanisms to evade caspase activation, while in neurodegenerative conditions, inappropriate caspase activity leads to the loss of vital neurons (StatPearls, 2023). Consequently, caspases and their associated pathways are significant therapeutic targets, with drug development focusing on both the inhibition of cell death in degenerative diseases and the induction of apoptosis in oncology (PubMed, 2021). The crosstalk between these pathways is mediated by proteins like Beclin-1 and Bcl-2, which regulate the switch between survival and death (Nature, 2020).

Other names

Cysteine-dependent aspartate-directed proteasesApoptotic proteasesCaspase-mediated pathwaysApoptosis-autophagy signaling

Caspase inhibitors typically bind to the active site of the enzyme, preventing the cleavage of substrates required for apoptosis or the maturation of pro-inflammatory cytokines like IL-1β (PubChem, 2024). In oncology, drugs may indirectly activate caspases by neutralizing anti-apoptotic proteins (e.g., BCL-2 inhibitors) or by inducing cellular stress that triggers the intrinsic apoptotic pathway (PubMed, 2023).