Non-canonical roles of NAMPT and PARP in inflammation

Nicotinamide adenine dinucleotide (NAD⁺) is the most important hydrogen carrier in cell redox reactions. It is involved in mitochondrial function and metabolism, circadian rhythm, the immune response and inflammation, DNA repair, cell division, protein-protein signaling, chromatin remodeling and epigenetics. Recently, NAD⁺ has been recognized as the molecule of life, since, by increasing NAD⁺ levels in old or sick animals, it is possible to improve their health and lengthen their lifespan. In this review, we summarize the contribution of NAD⁺ metabolism to inflammation, with special emphasis in the major NAD⁺ biosynthetic enzyme, nicotinamide phosphoribosyl transferase (NAMPT), and the NAD⁺-consuming enzyme, poly(ADP-ribose) polymerase (PARP). The extracurricular roles of these enzymes, i.e. the proinflammatory role of NAMPT after its release, and the ability of PARP to promote a novel form of cell death, known as parthanatos, upon hyperactivation are revised and discussed in the context of several chronic inflammatory diseases.