Figure 1.

NAD⁺ metabolism and points of pharmacological intervention.

Enzymes involved in NAD⁺ biosynthesis and hydrolysis play important roles in inflammation and immunity. Biosynthetic pathways include the NAD⁺ salvage pathway, which recycles nicotinamide to form NMN, then NAD⁺, and the de novo pathway that begins with tryptophan. Hydrolysis of NAD⁺ is largely carried out by PARPs, which tag target proteins with poly- or mono-(ADP ribose); sirtuins, which remove acyl groups and create O-acyl-ADP-ribose; and CD38, BST, and SARM1, which create (cyclic)-ADP-ribose [44]. There are multiple points of potential pharmacological intervention throughout NAD⁺ metabolic pathways. Created with BioRender.com. Abbreviations: i, inhibitor; NAMPT, nicotinamide phosphoribosyltransferase; NMN, nicotinamide mononucleotide; NR, nicotinamide ribose; NSP3, nonstructural protein 3; PARP, poly(ADP-ribose) polymerase; SARM1, sterile alpha and TIR motif containing 1; SIRT, sirtuin.