Necroptosis in amyotrophic lateral sclerosis and other neurological disorders

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons. Cell death in ALS and in general was previously believed to exist as a dichotomy between apoptosis and necrosis. Most research investigating cell death mechanisms in ALS was conducted before the discovery of programmed necrosis thus did not use selective cell death pathway-specific markers. Recently, a new form of programmed cell death, termed “necroptosis”, has been characterized and has been recently implicated in ALS as a primary mechanism driving motor neuron cell death in different forms of ALS. The present review is aimed at summarizing cell death pathways that are currently implicated in ALS and highlighting the emerging evidence on necroptosis as a major driver of motor neuron cell death. •Necroptosis contributes to motor neuron cell death in ALS.•Apoptosis, necroptosis, NLRP3 inflammasome and autophagy are all currently implicated in ALS.•A more thoroughly characterized cell death pathway is necessary in ALS.