Targeting NAD⁺ Metabolism as Interventions for Mitochondrial Disease.

ABSTRACT: Leigh syndrome is a mitochondrial disease characterized by neurological disorders, metabolic abnormality and premature death. There is no cure for Leigh syndrome; therefore, new therapeutic targets are urgently needed. In Ndufs4-KO mice, a mouse model of Leigh syndrome, we found that Complex I deficiency led to declines in NAD⁺ levels and NAD⁺ redox imbalance. We tested the hypothesis that elevation of NAD⁺ levels would benefit Ndufs4-KO mice. Administration of NAD⁺ precursor, nicotinamide mononucleotide (NMN) extended lifespan of Ndufs4-KO mice and attenuated lactic acidosis. NMN increased lifespan by normalizing NAD⁺ redox imbalance and lowering HIF1a accumulation in Ndufs4-KO skeletal muscle without affecting the brain. NMN up-regul

SUBMITTER: Lee CF 

PROVIDER: S-EPMC6395802 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature