[NAD.sup.+] metabolism in health and disease

Nicotinamide adenine dinucleotide ([NAD.sup.+]) is both a coenzyme for hydride-transfer enzymes and a substrate for [NAD.sup.+]-consuming enzymes, which include ADP-ribose transferases, poly(ADP-ribose) polymerases, cADP-ribose synthases and sirtuins. Recent results establish protective roles for [NAD.sup.+] that might be applicable therapeutically to prevent neurodegenerative conditions and to fight Candida glabrata infection. In addition, the contribution that [NAD.sup.+] metabolism makes to lifespan extension in model systems indicates that therapies to boost [NAD.sup.+] might promote some of the beneficial effects of calorie restriction. Nicotinamide riboside, the recently discovered nucleoside precursor of [NAD.sup.+] in eukaryotic systems, might have advantages as a therapy to elevate [NAD.sup.+] without inhibiting sirtuins, which is associated with high-dose nicotinamide, or incurring the unpleasant side-effects of high-dose nicotinic acid.