Brainiac Caspases: Beyond the Wall of Apoptosis.

Ana María Espinosa-Oliva,Isabel María Alonso-Bellido,Miguel Angel Burguillos,Juan García-Revilla

doi:10.3389/fncel.2019.00500

Abstract

For the last two decades, caspases, a family of cysteine-aspartic proteases, have evolved from being considered solely as regulators of apoptosis or inflammation to having a wider range of functions. In this mini review, we focus on the most recent “non-apoptotic” roles of caspases in the CNS, particularly in neurons, astrocytes and oligodendrocytes. Non-apoptotic caspase functions in microglia have already been reviewed extensively elsewhere. Here we discuss the involvement of caspases in the activation of the inflammasome, autophagy, and non-apoptotic forms of cell death such as necroptosis and pyroptosis. Also, we review the involvement of caspases in synapses and the processing of aggregates key to neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s diseases. Likewise, we mention the recently described involvement of caspases in mitochondrial biogenesis, which is a function independent of the enzymatic activity. We conclude discussing the relevance that “new” functions of caspases have in the CNS and the future of this field of research.

Highlights

Since the discovery of CED-3 in Caenorhabditis elegans (Ellis and Horvitz, 1986) and the caspase1/Interleukin-1 converting enzyme (ICE) (Thornberry et al, 1992; Yuan et al, 1993), caspases were grouped based on their function as “apoptotic” or “inflammatory.” This classification has remained useful to some extent until recently, since new non-apoptotic or non-inflammatory roles have surfaced for caspases (Shalini et al, 2015; Baena-Lopez et al, 2018; Hollville and Deshmukh, 2018)
Over the last decade, evidence has been gathered detailing non-apoptotic roles for caspases in astrocytes, neurons, oligodendrocytes (ODCs) and microglia (Acarin et al, 2007; Li et al, 2010; Burguillos et al, 2011; Wagner et al, 2011). The aim of this mini-review is to provide an update on the various functions of caspases in the CNS, focusing mainly on neurons, astrocytes and ODCs
Necroptosis was considered a passive death of cells under pathological conditions, where the cellular contents are released and cause an immune response. Currently it is considered a cell death pathway regulated through the interaction of different molecules including receptor-interacting protein kinase (RIPK)-1 and RIPK3, mixed lineage kinase domain-like protein (MLKL), and caspase-8 (Figure 1A; Tait et al, 2014; Ofengeim et al, 2015)

Summary

Introduction

Caspases are a family of proteins belonging to the cysteine aspartate proteases classically associated with different forms of programmed cell death (Stennicke and Salvesen, 1999; Hyman and Yuan, 2012; Tummers and Green, 2017).Since the discovery of CED-3 in Caenorhabditis elegans (Ellis and Horvitz, 1986) and the caspase1/Interleukin-1 converting enzyme (ICE) (Thornberry et al, 1992; Yuan et al, 1993), caspases were grouped based on their function as “apoptotic” or “inflammatory.” This classification has remained useful to some extent until recently, since new non-apoptotic or non-inflammatory roles have surfaced for caspases (Shalini et al, 2015; Baena-Lopez et al, 2018; Hollville and Deshmukh, 2018). The presence of different types of inflammasomes have been reported in non-immune related cells, such as neurons (Figure 1B and Table 1).

Results

Conclusion