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Research ArticlePERSPECTIVES IN PHARMACOLOGY

NAD+ and Vitamin B3: From Metabolism to Therapies

Anthony A. Sauve
Journal of Pharmacology and Experimental Therapeutics March 2008, 324 (3) 883-893; DOI: https://doi.org/10.1124/jpet.107.120758
Anthony A. Sauve
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Abstract

The role of NAD+ metabolism in health and disease is of increased interest as the use of niacin (nicotinic acid) has emerged as a major therapy for treatment of hyperlipidemias and with the recognition that nicotinamide can protect tissues and NAD+ metabolism in a variety of disease states, including ischemia/reperfusion. In addition, a growing body of evidence supports the view that NAD+ metabolism regulates important biological effects, including lifespan. NAD+ exerts potent effects through the poly(ADP-ribose) polymerases, mono-ADP-ribosyltransferases, and the recently characterized sirtuin enzymes. These enzymes catalyze protein modifications, such as ADP-ribosylation and deacetylation, leading to changes in protein function. These enzymes regulate apoptosis, DNA repair, stress resistance, metabolism, and endocrine signaling, suggesting that these enzymes and/or NAD+ metabolism could be targeted for therapeutic benefit. This review considers current knowledge of NAD+ metabolism in humans and microbes, including new insights into mechanisms that regulate NAD+ biosynthetic pathways, current use of nicotinamide and nicotinic acid as pharmacological agents, and opportunities for drug design that are directed at modulation of NAD+ biosynthesis for treatment of human disorders and infections.

Footnotes

  • This work has been supported in part by National Institutes of Health Grant DK 73466-01 (to A.S.).

  • A.S. is a consultant for Sirtris Pharmaceuticals and has financial interests related to some of the topics discussed in this review.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.107.120758.

  • ABBREVIATIONS: ADPR, adenosine diphosphate ribose; APP, amyloid precursor protein; NAMN, nicotinic acid mononucleotide; nampt, nicotinamide phosphoribosyltransferase; NMN, nicotinamide mononucleotide; nmnat, nicotinamide/nicotinate mononucleotide adenylyltransferase; NR, nicotinamide riboside; PARP, poly(ADP-ribose) polymerase; PBEF, pre-B-cell colony-enhancing factor; PRPP, 5-phosphoryl-ribose-1-pyrophosphate; QA, quinolinic acid; Sir2, silencing information regulator 2; HDL, high-density lipoprotein; SIRT1, mammalian sirtuin 1; FK-866, (E)-N-[4-(1-benzoylpiperidine-4-yl)butyl]-3-(pyridin-3-yl)acrylamide.

    • Received June 14, 2007.
    • Accepted December 27, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
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In this issue

Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticlePERSPECTIVES IN PHARMACOLOGY

NAD+ and Vitamin B3: From Metabolism to Therapies

Anthony A. Sauve
Journal of Pharmacology and Experimental Therapeutics March 1, 2008, 324 (3) 883-893; DOI: https://doi.org/10.1124/jpet.107.120758

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Research ArticlePERSPECTIVES IN PHARMACOLOGY

NAD+ and Vitamin B3: From Metabolism to Therapies

Anthony A. Sauve
Journal of Pharmacology and Experimental Therapeutics March 1, 2008, 324 (3) 883-893; DOI: https://doi.org/10.1124/jpet.107.120758
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  • Article
    • Abstract
    • NAD+ Metabolism
    • De Novo Pathways in Humans Microbes and Bacteria
    • Recycling in Bacteria
    • Recycling in Humans
    • Pathways Involving Nicotinamide Riboside
    • The Role of NAD in Energy Metabolism and Oxidation Processes
    • Clinical Manifestations of Niacin Deficiency
    • Prospects for Drugs Targeted to Inhibition of NAD+ Biosynthesis
    • Regulation of NAD in a Model Microbe: Yeast
    • Regulation of NAD+ Metabolism in Humans
    • Pharmacology of NAD+ Increasing Agents
    • Effects NA and NAM on NAD+ in Tissues
    • Genome Stability
    • Ischemia and Stroke
    • Nicotinamide in Fetal Ischemia and Fetal Alcohol Syndrome
    • Alzheimer's Disease and Neurodegenerative Disorders
    • Conclusions
    • Footnotes
    • References
  • Figures & Data
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