Evaluation of the NAD⁺ biosynthetic pathway in ALS patients and effect of modulating NAD⁺ levels in hSOD1-linked ALS mouse models.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons. Astrocytes from diverse ALS models induce motor neuron death in co-culture. Enhancing NAD⁺ availability, or increasing the expression of the NAD⁺-dependent deacylases SIRT3 and SIRT6, abrogates their neurotoxicity in cell culture models. To determine the effect of increasing NAD⁺ availability in ALS mouse models we used two strategies, ablation of a NAD⁺-consuming enzyme (CD38) and supplementation with a bioavailable NAD⁺ precursor (nicotinamide riboside, NR). Deletion of CD38 had no effect in the survival of two hSOD1-linked ALS mouse models. On the other hand, NR-supplementation delayed motor neuron degeneration, decreased markers of ne

SUBMITTER: Harlan BA 

PROVIDER: S-EPMC7089832 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature