Necroptosis is dispensable for motor neuron degeneration in a mouse model of ALS.

ABSTRACT: Motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is proposed to occur by necroptosis, an inflammatory form of regulated cell death. Prior studies implicated necroptosis in ALS based on accumulation of necroptotic markers in affected tissues of patients and mouse models, and amelioration of disease in mutant superoxide dismutase 1 (SOD1^G93A) mice with inhibition of the upstream necroptotic mediators, receptor interacting protein kinase 1 (RIPK1), and RIPK3. To definitively address the pathogenic role of necroptosis in ALS, we genetically ablated the critical terminal executioner of necroptosis, mixed lineage kinase domain-like protein (MLKL), in SOD1^G93A mice. Disease onset, progression, and survival were not affected in SOD1^G93A mice lacking

SUBMITTER: Wang T 

PROVIDER: S-EPMC7206015 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature