Abstract
Caspases are a family of cysteine proteases that predominantly cleave their substrates after aspartic acid residues. Much of what we know of caspases emerged from investigation a highly conserved form of programmed cell death called apoptosis. This form of cell death is regulated by several caspases, including caspase-2, caspase-3, caspase-7, caspase-8 and caspase-9. However, these “killer” apoptotic caspases have emerged as versatile enzymes that play key roles in a wide range of non-apoptotic processes. Much of what we understand about these non-apoptotic roles is built on work investigating how “killer” caspases control a range of neuronal cell behaviors. This review will attempt to provide an up to date synopsis of these roles.
Highlights
The process of apoptosis, a type of programmed cell death, is understood in some detail (Figure 1)
It was the realization that apoptotic cell death in the nematode Caenorhabditis elegans relied on a caspase called CED-3 (Yuan, 1993) (Figure 2) that led to the discovery of mammalian apoptotic caspases and the elucidation of the molecular pathways that cause cell death (Figure 1)
Analysis of the substrates revealed a disproportionately high level of proteins found in extracellular vesicles (EVs), a finding corroborated by proteomic analysis of EVs from the auditory brainstem
Summary
The process of apoptosis, a type of programmed cell death, is understood in some detail (Figure 1). The first caspase identified, caspase-1 plays a central role in inflammation, processing prointerleukin-1β to its mature form and inducing pyroptosis (Fink and Cookson, 2006), a form of necrotic cell death. Roles for caspases typically associated with cell killing were identified in several types of cell differentiation, including the differentiation of neurons. These discoveries fundamentally altered how “killer” caspases were viewed. Non-Canonical Roles of Apoptotic Caspases non-canonical activity of apoptotic pathways in the nervous system, describing the relevant processes and where possible the signals that activate caspases, the regulation of caspase activity that prevents cell death and the substrates cleaved during non-apoptotic processes.
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