NAD+ and vitamin B3: from metabolism to therapies

J Pharmacol Exp Ther. 2008 Mar;324(3):883-93. doi: 10.1124/jpet.107.120758. Epub 2007 Dec 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • NAD / genetics
  • NAD / metabolism*
  • NAD / physiology
  • Niacinamide / analogs & derivatives
  • Niacinamide / genetics
  • Niacinamide / metabolism*
  • Niacinamide / physiology
  • Niacinamide / therapeutic use*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • nicotinamide-beta-riboside
  • NAD
  • Niacinamide