NAD+ metabolism-based immunoregulation and therapeutic potential

Nicotinamide adenine dinucleotide (NAD(+)) is a critical metabolite that acts as a cofactor in energy metabolism, and serves as a cosubstrate for non-redox NAD(+)-dependent enzymes, including sirtuins, CD38 and poly(ADP-ribose) polymerases. NAD(+) metabolism can regulate functionality attributes of innate and adaptive immune cells and contribute to inflammatory responses. Thus, the manipulation of NAD(+) bioavailability can reshape the courses of immunological diseases. Here, we review the basics of NAD(+) biochemistry and its roles in the immune response, and discuss current challenges and the future translational potential of NAD(+) research in the development of therapeutics for inflammatory diseases, such as COVID-19.