Nicotinamide adenine dinucleotide (NAD+) (NAD+)

Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme found in all living cells, essential for energy metabolism and a variety of regulatory processes [1, 2]. It exists in two forms: an oxidized form (NAD+) and a reduced form (NADH), acting as a key electron carrier in redox reactions such as glycolysis and the citric acid cycle [2]. Beyond its role in metabolism, NAD+ serves as a critical substrate for enzymes like sirtuins, poly(ADP-ribose) polymerases (PARPs), and cADP-ribose synthases (e.g., CD38), which regulate DNA repair, gene expression, and calcium signaling [3, 4]. Systemic decline in NAD+ levels is associated with aging and various age-related pathologies, including neurodegenerative diseases, metabolic disorders, and cardiovascular decline [3, 4]. Consequently, therapeutic strategies aim to restore NAD+ levels through precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) or by inhibiting NAD+-consuming enzymes like CD38 [5, 6, 9]. Conversely, in oncology, inhibiting NAD+ biosynthesis (e.g., via NAMPT inhibitors) is explored to starve cancer cells of energy and DNA repair capacity [7, 8]. Citations: [1] Bogan KL, Brenner C. Annu Rev Nutr. 2008;28:115-30. [2] Cantó C, et al. Cell Metab. 2015;22(1):31-53. [3] Verdin E. Science. 2015;350(6265):1208-13. [4] Imai S, Guarente L. Trends Cell Biol. 2014;24(8):464-71. [5] Martens CR, et al. Nat Commun. 2018;9(1):1286. [6] Yoshino J, et al. Cell Metab. 2011;14(4):528-36. [7] Lord CJ, Ashworth A. Science. 2017;355(6330):1152-1158. [8] Nahimana A, et al. Blood. 2009;113(14):3276-86. [9] Escande C, et al. Diabetes. 2013;62(4):1084-93.

Other names

NAD+ metabolismNAD+ homeostasisNAD+ signalingSystemic NAD+-dependent cellular processes

Modulation of NAD+ levels through precursor supplementation (NR, NMN), inhibition of NAD+ salvage pathways (NAMPT inhibitors), inhibition of NAD+ degradation (CD38 inhibitors), or competitive inhibition of NAD+-dependent enzymes (PARP inhibitors).