Physiological functions of non-apoptotic caspase activity in the nervous system

Abstract

Caspases are cysteine proteases that play important and well-defined roles in apoptosis and inflammation. Increasing evidence point to alternative functions of caspases where restricted and localized caspase activation within neurons allows for a variety of non-apoptotic and non-inflammatory processes required for brain development and function. In this review, we highlight sublethal caspase functions in axon and dendrite pruning, neurite outgrowth and dendrite branches formation, as well as in long-term depression and synaptic plasticity. Importantly, as non-apoptotic activity of caspases is often confined in space and time in neurons, we also discuss the mechanisms that restrict caspase activity in order to maintain the neuronal networks in a healthy and functional state.

Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent apoptosis pathway

“…Mitochondrion-dependent activation of caspases contributes not only to removal of unnecessary cells during development or damaged cells exposed to stress stimuli but also to regulation of tissue stem cell differentiation and terminal differentiation of myoblasts, erythroblasts and keratinocytes (Hollville and Deshmukh, 2017). Furthermore, non-apoptotic caspase activation plays a key regulatory role in the pruning of neurites and the formation and maturation of neural circuits in the nervous system (Unsain and Barker, 2015).…”

Nucleolar control by a non‐apoptotic p53‐caspases‐deubiquitinylase axis promotes resistance to bacterial infection

“…Our present work substantiated this link by dissecting a key underlying pathway, which initiates from the stress sensor p53/CEP-1 to antagonize the nucleolar USP36/USP-33-fibrillarin/FIB-1 regulatory network and ultimately activates antimicrobial peptide genes expression. 60 Importantly, as one of the ancient caspases in animals, CED-3 is the sole caspase encoded by C. elegans and presumably endowed with the manifold cellular roles not yet diversified by evolution. However, how the downregulation of fibrillarin contributes to upregulation of saposin-like family genes and the associated innate immune responses remains unresolved at present.…”

“…7,9 In other organisms, distinct members of the caspase family have also been functionally linked to inflammasome formation, 58 embryonic stem cell differentiation, 59 and neuron outgrowth, guidance attraction, and branching. 60 Importantly, as one of the ancient caspases in animals, CED-3 is the sole caspase encoded by C. elegans and presumably endowed with the manifold cellular roles not yet diversified by evolution. This notion of "multitasker" is evidently supported by our study, which illustrated CED-3's roles in both innate immunity and nucleolus control.…”

Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent pathway of apoptosis

“…Mitochondrion-dependent activation of caspases contributes not only to removal of unnecessary cells during development or damaged cells exposed to stress stimuli but also to regulation of tissue stem cell differentiation and terminal differentiation of myoblasts, erythroblasts, and keratinocytes (Hollville and Deshmukh, 2017). Furthermore, nonapoptotic caspase activation plays a key regulatory role in the pruning of neurites and the formation and maturation of neural circuits in the nervous system (Unsain and Barker, 2015).…”