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Neurochem Res. 2019 May 7. doi: 10.1007/s11064-019-02809-1. [Epub ahead of print]

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

Author information

1
Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 1400 York Street, 5th Floor, Room A-501, New York, NY, 10065, USA. alejandro.lloret@neucyte.com.
2
NeuCyte Pharmaceuticals, 1561 Industrial Road, San Carlos, CA, 94070, USA. alejandro.lloret@neucyte.com.
3
Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 1400 York Street, 5th Floor, Room A-501, New York, NY, 10065, USA.

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.

KEYWORDS:

Huntington’s disease; NAD+; Nicotinamide Riboside; PARPs; PGC-1 alpha; Sirtruins

PMID:
31065944
DOI:
10.1007/s11064-019-02809-1

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