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PGC-1α, Sirtuins and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All

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Abstract

In this review, we summarize the available published information on the neuroprotective effects of increasing nicotinamide adenine dinucleotide (NAD+) levels in Huntington’s disease models. We discuss the rationale of potential therapeutic benefit of administering nicotinamide riboside (NR), a safe and effective NAD+ precursor. We discuss the agonistic effect on the Sirtuin1-PGC-1α-PPAR pathway as well as Sirtuin 3, which converge in improving mitochondrial function, decreasing ROS production and ameliorating bioenergetics deficits. Also, we discuss the potential synergistic effect of increasing NAD+ combined with PARPs inhibitors, as a clinical therapeutic option not only in HD, but other neurodegenerative conditions.

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Acknowledgements

We are grateful for the support of NINDS grant 5R01NS086746-04.

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Lloret, A., Beal, M.F. PGC-1α, Sirtuins and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All. Neurochem Res 44, 2423–2434 (2019). https://doi.org/10.1007/s11064-019-02809-1

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