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Caspase-independent cell death

Abstract

Caspase activation has been frequently viewed as synonymous with apoptotic cell death; however, caspases can also contribute to processes that do not culminate in cell demise. Moreover, inhibition of caspases can have cytoprotective effects. In a number of different models, caspase inhibition does not maintain cellular viability and instead shifts the morphology of death from apoptosis to nonapoptotic pathways. Here, we explore the contribution of caspases to cell death, either as upstream signals or as downstream effectors contributing to apoptotic morphology, as well as alternative strategies for cell death inhibition. Such alternative strategies may either target catabolic hydrolases or be aimed at preventing mitochondrial membrane permeabilization and its upstream triggers.

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Figure 1: Major pathways to caspase-dependent and caspase-independent cell death.
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Acknowledgements

G.K. is supported by Ligue Nationale contre le cancer, European Union (Active p53, Impaled, RIGHT, Trans-Death), Canceropole Ile-de-France, and French Ministry of Science. S.J.M. is supported by a Principal Investigator Award from Science Foundation Ireland.

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Correspondence to Guido Kroemer.

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Kroemer, G., Martin, S. Caspase-independent cell death. Nat Med 11, 725–730 (2005). https://doi.org/10.1038/nm1263

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