Neurons undergo pathogenic metabolic reprogramming in models of familial ALS.

ABSTRACT:

Objectives

Normal cellular function requires a rate of ATP production sufficient to meet demand. In most neurodegenerative diseases (including Amyotrophic Lateral Sclerosis [ALS]), mitochondrial dysfunction is postulated raising the possibility of impaired ATP production and a need for compensatory maneuvers to sustain the ATP production/demand balance. We investigated intermediary metabolism of neurons expressing familial ALS (fALS) genes and interrogated the functional consequences of glycolysis genes in fitness assays and neuronal survival.

Methods

We created a pure neuronal model system for isotopologue investigations of fuel utilization. In a yeast platform we studied the functional contributions of glycolysis genes in a growth fitness assay iafter expressing of a fALS

SUBMITTER: Riechers SP 

PROVIDER: S-EPMC8958550 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature