Brainiac Caspases: Beyond the Wall of Apoptosis

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.

Neuroprotective Effects of Necrostatin-1 Against Oxidative Stress–Induced Cell Damage: an Involvement of Cathepsin D Inhibition

“…Finally, we confirmed in RA-SH-SY5Y cells the H 2 O 2 potency to induce ICE-like protease, caspase-1 activity (Jantas et al 2018a) which was significantly attenuated only by Nec-1 + Curc combination (Table 3). Activation of this enzyme participates in another form of cell damage, namely pyroptosis (Espinosa-Oliva et al 2019;Wang et al 2019). Since previous data showed the activation of this proinflammatory protease in neuronal cell type, including SH-SY5Y cells and neuroprotective potency of its inhibitors (Chen et al 2019;Knaryan et al 2014;Nath et al 1996;Zhao et al 2019a, b), it is highly probable that this mechanisms could be responsible for synergistic protective action of Nec-1 and curcumin against H 2 O 2 -evoked cell damage, observed in the present study.…”

The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells

“…Caspases are a family of endonucleases that act as critical links in the molecular networks that control apoptosis and play critical roles in the induction of apoptosis as both initiators (caspase-2, -8, -9, -10, 20, and -22) and executioners (caspase-3, -6, -7, and 21) [ 50 , 51 ]. Caspases are initially expressed as inactive procaspases that are activated by pro-apoptotic signals via proteolytic cleavage.…”

Mogroside IIe Ameliorates Cardiomyopathy by Suppressing Cardiomyocyte Apoptosis in a Type 2 Diabetic Model

“…Studies have shown that the caspase family plays an important role in apoptosis execution ( Wang et al, 2019 ). Caspase-3 constitutes the central molecule in apoptosis and is involved in three main pathways: the exogenous death receptor pathway, endogenous mitochondrial pathway, and endoplasmic reticulum pathway ( Espinosa-Oliva et al, 2019 ). The exogenous death receptor pathway is triggered by a transmembrane protein reaction caused by TNF-α, and mainly involves caspase-8, a pro-apoptotic factor ( DeLaney et al, 2019 ).…”