MicroRNAs as regulators of cell death mechanisms in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons (MNs), resulting in paralysis and precocious death from respiratory failure. Although the causes of ALS are incompletely understood, the role of alterations in RNA metabolism seems central. MicroRNAs (miRNAs) are noncoding RNAs implicated in the regulation of gene expression of many relevant physiological processes, including cell death. The recent model of programmed cell death (PCD) encompasses different mechanisms, from apoptosis to regulated necrosis (RN), in particular necroptosis. Both apoptosis and necroptosis play a significant role in the progressive death of MNs in ALS. In this review, we present key research related to miRNAs that modulate apoptosis and RN pathways in ALS. We also discuss whether these miRNAs represent potential targets for therapeutic development in patients.