Neuronal mitochondrial dysfunction in sporadic amyotrophic lateral sclerosis is developmentally regulated.

ABSTRACT: Amyotrophic lateral sclerosis is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Mitochondria are essential for neuronal survival but the developmental timing and mechanistic importance of mitochondrial dysfunction in sporadic ALS (sALS) neurons is not fully understood. We used human induced pluripotent stem cells and generated a developmental timeline by differentiating sALS iPSCs to neural progenitors and to motor neurons and comparing mitochondrial parameters with familial ALS (fALS) and control cells at each developmental stage. We report that sALS and fALS motor neurons have elevated reactive oxygen species levels, depolarized mitochondria, impaired oxidative phosphorylation, ATP loss and defective mitochondrial protein import compared with control mo

SUBMITTER: Singh T 

PROVIDER: S-EPMC8460779 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature