NAD+ and vitamin B3: from metabolism to therapies.
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.
Sauve
Anthony A
AA
Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. aas2004@med.cornell.edu
D000818:Animals; D006801:Humans; D009243:NAD / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism* / Q000502:physiology / Q000627:therapeutic use*; D011726:Pyridinium Compounds; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D011726:Pyridinium Compounds; C018613:nicotinamide-beta-riboside; D009243:NAD; D009536:Niacinamide