Nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH are essential coupled redox metabolites that primarily promote cellular oxidative (catabolic) metabolic reactions. This enables energy generation through glycolysis and mitochondrial respiration to support cell growth and survival. In addition, many key enzymes that regulate diverse cell functions ranging from gene expression to proteostasis require NAD+ as a co-substrate for their catalytic activity. This includes the NAD+-dependent sirtuin family of protein deacetylases and the PARP family of DNA repair enzymes. Whilst their vital activity consumes NAD+ which is cleaved to nicotinamide, several pathways exist for re-generating NAD+ and sustaining NAD+ homeostasis. However, there is growing evidence of perturbed NAD+ homeostasis and NAD+-regulated processes contributing to multiple disease states. NAD+ levels decline in the human brain and other organs with age and this is associated with neurodegeneration and other age-related diseases. Dietary supplementation with NAD+ precursors is being investigated to counteract this. Paradoxically, many cancers have increased dependency on NAD+. Clinical efforts to exploit this have so far shown limited success. Emerging new opportunities to exploit dysregulation of NAD+ metabolism in cancers are critically discussed. An update is also provided on other key NAD+ research including perturbation of the NAD+ salvage enzyme NAMPT in the context of the tumour microenvironment (TME), methodology to study subcellular NAD+ dynamics in real-time and the regulation of differentiation by competing NAD+ pools.
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June 2020
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SMAD-dependent and SMAD-independent BMP9 signalling pathways during osteogenesis. For more information, see the article by Liu and colleagues in this issue (pp. 1269–1268). The image was provided by Dingming Huang.
Review Article|
June 23 2020
Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target
Hollie B.S. Griffiths;
Hollie B.S. Griffiths
School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, U.K.
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Courtney Williams;
Courtney Williams
School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, U.K.
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Sarah J. King;
Sarah J. King
School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, U.K.
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Simon J. Allison
School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, U.K.
Correspondence: Simon J. Allison ([email protected])
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Publisher: Portland Press Ltd
Received:
May 13 2020
Revision Received:
May 29 2020
Accepted:
June 01 2020
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem Soc Trans (2020) 48 (3): 733–744.
Article history
Received:
May 13 2020
Revision Received:
May 29 2020
Accepted:
June 01 2020
Citation
Hollie B.S. Griffiths, Courtney Williams, Sarah J. King, Simon J. Allison; Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target. Biochem Soc Trans 30 June 2020; 48 (3): 733–744. doi: https://doi.org/10.1042/BST20190033
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