Abstract
Cell death related (CDR) proteins are a diverse group of proteins whose original function was ascribed to apoptotic cell death signaling. Recently, descriptions of non-apoptotic functions for CDR proteins have increased. In this minireview, we comment on recent studies of CDR proteins outside the field of apoptosis in the CNS, encompassing areas such as the inflammasome and non-apoptotic cell death, cytoskeleton reorganization, synaptic plasticity, mitophagy, neurodegeneration and calcium signaling among others. Furthermore, we discuss the evolution of proteomic techniques used to predict caspase substrates that could potentially explain their non-apoptotic roles. Finally, we address new concepts in the field of non-apoptotic functions of CDR proteins that require further research such the effect of sexual dimorphism on non-apoptotic CDR protein function and the emergence of zymogen-specific caspase functions.
Highlights
Cell death related (CDR) proteins include a variety of proteins (e.g. caspases, members of the Bcl-2 family, etc.) whose actions directly affect the outcome of the apoptotic cell death (i.e. pro-apoptotic vs. anti-apoptotic proteins)
Cell death related (CDR) proteins include a variety of proteins whose actions directly affect the outcome of the apoptotic cell death
An increase in the expression of inflammasome components in aged female rats compared to aged-match males was linked to their decrease in estrogen levels (Raval et al, 2019). These results suggest that the inclusion of both genders in future studies of non-apoptotic roles for caspase and other CDR proteins should be taken into consideration
Summary
CDR proteins include a variety of proteins (e.g. caspases, members of the Bcl-2 family, etc.) whose actions directly affect the outcome of the apoptotic cell death (i.e. pro-apoptotic vs. anti-apoptotic proteins). Some of the first non-apoptotic functions described for caspases were linked to inflammatory processes, and alternative cell death pathways, pyroptosis and necroptosis. There is a study that suggests that caspase-6, implicated in axonal degeneration and cognitive decline in AD (Simon et al, 2012; Geden et al, 2019), may play an additional role in inflammasome activation in neurons (Kaushal et al, 2015).
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