Modulating NAD Metabolism, from Bench To bedside

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2017 Aug 9

PMID 28784597

Citations 106

Authors

Elena Katsyuba

Johan Auwerx

Affiliations

Soon will be listed here.

Abstract

Discovered in the beginning of the 20 century, nicotinamide adenine dinucleotide (NAD) has evolved from a simple oxidoreductase cofactor to being an essential cosubstrate for a wide range of regulatory proteins that include the sirtuin family of NAD-dependent protein deacylases, widely recognized regulators of metabolic function and longevity. Altered NAD metabolism is associated with aging and many pathological conditions, such as metabolic diseases and disorders of the muscular and neuronal systems. Conversely, increased NAD levels have shown to be beneficial in a broad spectrum of diseases. Here, we review the fundamental aspects of NAD biochemistry and metabolism and discuss how boosting NAD content can help ameliorate mitochondrial homeostasis and as such improve healthspan and lifespan.

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References

Camacho-Pereira J, Tarrago M, Chini C, Nin V, Escande C, Warner G . CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016; 23(6):1127-1139. PMC: 4911708. DOI: 10.1016/j.cmet.2016.05.006. View

Yin T, Britt J, De Jesus-Cortes H, Lu Y, Genova R, Khan M . P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury. Cell Rep. 2014; 8(6):1731-1740. PMC: 4206693. DOI: 10.1016/j.celrep.2014.08.030. View

Escande C, Nin V, Price N, Capellini V, Gomes A, Barbosa M . Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2012; 62(4):1084-93. PMC: 3609577. DOI: 10.2337/db12-1139. View

Klaidman L, Morales M, Kem S, Yang J, Chang M, Adams Jr J . Nicotinamide offers multiple protective mechanisms in stroke as a precursor for NAD+, as a PARP inhibitor and by partial restoration of mitochondrial function. Pharmacology. 2003; 69(3):150-7. DOI: 10.1159/000072668. View

Wojcik M, Seidle H, Bieganowski P, Brenner C . Glutamine-dependent NAD+ synthetase. How a two-domain, three-substrate enzyme avoids waste. J Biol Chem. 2006; 281(44):33395-402. DOI: 10.1074/jbc.M607111200. View

Xie L, Wang Z, Li C, Yang K, Liang Y . Protective effect of nicotinamide adenine dinucleotide (NAD) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis. J Clin Neurosci. 2016; 36:114-119. DOI: 10.1016/j.jocn.2016.10.038. View

Reinhard Jr J . Altered tryptophan metabolism in mice with herpes simplex virus encephalitis: increases in spinal cord quinolinic acid. Neurochem Res. 1998; 23(5):661-5. DOI: 10.1023/a:1022438822023. View

Zhang X, Kurnasov O, Karthikeyan S, Grishin N, Osterman A, Zhang H . Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. J Biol Chem. 2003; 278(15):13503-11. DOI: 10.1074/jbc.M300073200. View

Pirinen E, Canto C, Jo Y, Morato L, Zhang H, Menzies K . Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab. 2014; 19(6):1034-41. PMC: 4047186. DOI: 10.1016/j.cmet.2014.04.002. View

10.

Fulco M, Cen Y, Zhao P, Hoffman E, McBurney M, Sauve A . Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell. 2008; 14(5):661-73. PMC: 2431467. DOI: 10.1016/j.devcel.2008.02.004. View

11.

Collins P, Chaykin S . The management of nicotinamide and nicotinic acid in the mouse. J Biol Chem. 1972; 247(3):778-83. View

12.

Katsyuba E, Auwerx J . Modulating NAD metabolism, from bench to bedside. EMBO J. 2017; 36(18):2670-2683. PMC: 5599801. DOI: 10.15252/embj.201797135. View

13.

Sadanaga-Akiyoshi F, Yao H, Tanuma S, Nakahara T, Hong J, Ibayashi S . Nicotinamide attenuates focal ischemic brain injury in rats: with special reference to changes in nicotinamide and NAD+ levels in ischemic core and penumbra. Neurochem Res. 2003; 28(8):1227-34. DOI: 10.1023/a:1024236614015. View

14.

Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F . SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008; 134(2):317-28. DOI: 10.1016/j.cell.2008.06.050. View

15.

WILLIAMS Jr J, FEIGELSON P, ELVEHJEM C . Relation of tryptophan and niacin to pyridine nucleotides of tissue. J Biol Chem. 1950; 187(2):597-604. View

16.

Collins P, Chaykin S . Comparative metabolism of nicotinamide and nicotinic acid in mice. Biochem J. 1971; 125(4):117P. PMC: 1178340. DOI: 10.1042/bj1250117pa. View

17.

Barbosa M, Soares S, Novak C, Sinclair D, Levine J, Aksoy P . The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. FASEB J. 2007; 21(13):3629-39. DOI: 10.1096/fj.07-8290com. View

18.

Satoh A, Stein L, Imai S . The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Handb Exp Pharmacol. 2011; 206:125-62. PMC: 3745303. DOI: 10.1007/978-3-642-21631-2_7. View

19.

Swarbrick J, Graeff R, Zhang H, Thomas M, Hao Q, Potter B . Cyclic adenosine 5'-diphosphate ribose analogs without a "southern" ribose inhibit ADP-ribosyl cyclase-hydrolase CD38. J Med Chem. 2014; 57(20):8517-29. PMC: 4207131. DOI: 10.1021/jm501037u. View

20.

Trammell S, Weidemann B, Chadda A, Yorek M, Holmes A, Coppey L . Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Sci Rep. 2016; 6:26933. PMC: 4882590. DOI: 10.1038/srep26933. View