Using metabolic screening, Allen et al. identify an adenosine to inosine deamination defect in astrocytes from ALS patients. This defect is the result of reduced expression of adenosine deaminase, leading to increased susceptibility to adenosine-mediated toxicity. Astrocyte inosine supplementation reverses the motor neuron toxicity observed with patient astrocytes in co-culture.

Energy metabolism is altered in amyotrophic lateral sclerosis and its animal models. Using metabolic profiling, Allen et al. reveal a loss of metabolic flexibility in induced astrocytes derived from patients with C9orf72 ALS, caused by defects in glycogen, fructose and mitochondrial energy substrate transport.

Highlights Aging affects the metabolic profile of fibroblasts derived from ALS cases Increased NADH metabolism with age is observed in the presence of a specific set of catabolic energy substrates in healthy individuals Reduced NADH metabolism with age is observed in the presence of glycogen in the ALS cohort Disease progression rates in ALS cases correlate with fibroblast NADH production in the presence of a number of energy substrates including inosine

No abstract