NAD⁺ dyshomeostasis in RYR1-related myopathies.

ABSTRACT: Pathogenic variants in RYR1 cause a spectrum of rare congenital myopathies associated with intracellular calcium dysregulation. Glutathione redox imbalance has been reported in several Ryr1 disease model systems and clinical studies. NAD+ and NADP are essential cofactors in cellular metabolism and redox homeostasis. NAD+ deficiency has been associated with skeletal muscle bioenergetic deficits in mitochondrial myopathy and sarcopenia. Using a new colorimetric assay and large control dataset (n = 299), we assessed redox balance (glutathione, NAD+, and NADP) in whole blood from 28 RYR1-RM affected individuals (NCT02362425). Analyses were expanded to human skeletal muscle (n = 4), primary myotube cultures (n = 5), and whole blood and skeletal muscle specimens from Ryr1 Y524S mice. The in vitr

SUBMITTER: Lawal TA 

PROVIDER: S-EPMC12374369 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature