Caspase Activity and Regulation in Cell Death Mechanisms

Caspases are a family of cysteine-dependent proteases that orchestrate programmed cell death and inflammatory responses. They initiate apoptosis through a cascade of limited proteolysis, dismantling cellular components in a tightly regulated sequence, and mediate lytic death programmes such as pyroptosis by activating pore-forming effectors. Caspases are synthesised as inactive zymogens and activated via proteolytic cleavage within multiprotein complexes, including apoptosomes and inflammasomes. Their activity is controlled by adaptor proteins, post-translational modifications and endogenous inhibitors, ensuring spatial and temporal precision. Dysregulation of caspase activation underlies many pathological states, from neurodegeneration to cancer and autoinflammatory syndromes. Understanding the structural basis of substrate recognition, activation mechanisms and regulatory checkpoints has profound implications for the development of caspase-targeted therapies and diagnostic tools.

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Caspase Activity and Regulation in Cell Death Mechanisms publication trend

The graph below shows the total number of articles in caspase activity and regulation in cell death mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Apoptosis: A form of programmed cell death characterised by cell shrinkage, chromatin condensation and membrane blebbing without provoking inflammation.

Pyroptosis: An inflammatory mode of cell death driven by caspase-mediated cleavage of gasdermin family proteins, resulting in pore formation and release of proinflammatory contents.

Inflammasome: A multiprotein complex that activates inflammatory caspases in response to pathogen- or damage-associated molecular patterns.

Substrate specificity: The propensity of a caspase’s active site and exosite to recognise and cleave particular amino acid sequences in target proteins.

Exosite: An auxiliary binding region distinct from the catalytic site that enhances substrate recognition and cleavage efficiency.

References

1. Caspases: structural and molecular mechanisms and functions in cell death, innate immunity, and disease. Cell Discovery (2025).
2. Inflammatory caspase substrate specificities. mBio (2024).
3. A Comprehensive Exploration of Caspase Detection Methods: From Classical Approaches to Cutting-Edge Innovations. International Journal of Molecular Sciences (2024).
4. Extensive peptide and natural protein substrate screens reveal that mouse caspase-11 has much narrower substrate specificity than caspase-1. Journal of Biological Chemistry (2018).