Accumulating evidence indicates that NAD+ — a coenzyme for several enzymes, with a critical role in mitochondrial energy production — confers protection against ageing and numerous diseases. Using Caenorhabditis elegans and cell lines, Katsyuba et al. identify α-amino-β-carboxymuconate-ɛ-semialdehyde decarboxylase (ACMSD) as a key regulator of the de novo NAD+ synthesis pathway. Knockdown of ACMSD boosted NAD+ levels, increased sirtuin 1 activity and enhanced mitochondrial function. In mice, the ACMSD inhibitors TES-991 and TES-1025 increased tissue NAD+ levels and protected hepatic and renal function in models of nonalcoholic fatty liver disease and acute kidney injury, respectively.
References
Katsyuba, E. et al. De novo NAD+ synthesis enhances mitochondrial function and improves health. Nature https://doi.org/10.1038/s41586-018-0645-6 (2018)
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Crunkhorn, S. Promoting NAD+ production. Nat Rev Drug Discov 17, 864 (2018). https://doi.org/10.1038/nrd.2018.212
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DOI: https://doi.org/10.1038/nrd.2018.212
