Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target

Griffiths, Hollie B. S.; Williams, Courtney; King, Sarah; Allison, Simon J.

doi:10.1042/bst20190033

Cited by 35 publications

(27 citation statements)

References 118 publications

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“…On the other hand, NAD + is involved in cell bioenergetics, redox regulation, signaling, homeostasis, adaptive response to stress, and survival [14,15]. Specifically, different NAD +dependent enzymes are implicated in mechanisms regulating synaptic plasticity [16,17] and neuronal resilience to stress [18,19].…”

Section: Introductionmentioning

confidence: 99%

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

et al. 2021

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Charcot first described amyotrophic lateral sclerosis (ALS) between 1865 and 1874 as a sporadic adult disease resulting from the idiopathic progressive degeneration of the motor neuronal system, resulting in rapid, progressive, and generalized muscle weakness and atrophy. There is no cure for ALS and no proven therapy to prevent it or reverse its course. There are two drugs specifically approved for the treatment of ALS, riluzol and edaravone, and many others have already been tested or are following clinical trials. However, at the present moment, we still cannot glimpse a true breakthrough in the treatment of this devastating disease. Nevertheless, our understanding of the pathophysiology of ALS is constantly growing. Based on this background, we know that oxidative stress, alterations in the NAD+-dependent metabolism and redox status, and abnormal mitochondrial dynamics and function in the motor neurons are at the core of the problem. Thus, different antioxidant molecules or NAD+ generators have been proposed for the therapy of ALS. This review analyzes these options not only in light of their use as individual molecules, but with special emphasis on their potential association, and even as part of broader combined multi-therapies.

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Section: Introductionmentioning

confidence: 99%

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

et al. 2021

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“…As PARP-1 consumes NAD, which is the substrate for its activation (30), HBV-positive liver cancer cells may become sensitive to NAD deficiency triggered by NAMPT inhibition. Furthermore, sirtuins are a family of NAD-dependent deacetylases that have been shown to regulate numerous biological functions, including lipid and energy metabolism, DNA damage, oxidative stress and cell growth, survival and death (31)(32)(33). Sirtuin 6 promotes the transcription and replication of HBV by upregulating the expression of peroxisome proliferator-activated receptor α (34).…”

Section: Discussionmentioning

confidence: 99%

NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis

Guo

Chen

et al. 2021

Oncol Lett

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Nicotinamide phosphoribosyltransferase (NAMPT) is a critical rate-limiting enzyme involved in NAD synthesis that has been shown to contribute to the progression of liver cancer. However, the potential role and mechanism of NAMPT in hepatitis B virus (HBV)-associated liver cancer remain unclear. The present study assessed the expression of NAMPT in HBV-positive and-negative liver cancer cells, and investigated whether HBV-induced NAMPT expression is dependent on HBV X protein (HBx). In addition, the role of NAMPT in HBV replication and transcription, and in HBV-mediated liver cancer cell growth was explored. The effects of NAMPT on the glycolytic pathway were also evaluated. Reverse transcription-quantitative PCR and western blotting results revealed that NAMPT expression levels were significantly higher in HBV-positive liver cancer cells than in HBV-negative liver cancer cells, and this effect was HBx-dependent. Moreover, the activation of NAMPT was demonstrated to be required for HBV replication and transcription. The NAMPT inhibitor FK866 repressed cell survival and promoted cell death in HBV-expressing liver cancer cells, and these effects were attenuated by nicotinamide mononucleotide. Furthermore, the inhibition of NAMPT was associated with decreased glucose uptake, decreased lactate production and decreased ATP levels in HBV-expressing liver cancer cells, indicating that NAMPT may promote the aerobic glycolysis. Collectively, these findings reveal a positive feedback loop in which HBV enhances NAMPT expression and the activation of NAMPT promotes HBV replication and HBV-mediated malignant cell growth in liver cancer. The present study highlights the important role of NAMPT in the regulation of aerobic glycolysis in HBV-mediated liver cancer, and suggests that NAMPT may be a promising treatment target for patients with HBV-associated liver cancer.

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“…As electron carriers, nicotinamide adenine dinucleotides (NAD and NADH) play essential roles, directly and indirectly, in numerous biological processes in both eukaryotes and bacteria [79][80][81]. During bacterial aerobic respiration, NAD+ is reduced to NADH through glycolysis and the tricarboxylic acid (TCA) cycle [82].…”

Section: Sensing Nad+/nadh: Rexmentioning

confidence: 99%

How Bacterial Redox Sensors Transmit Redox Signals via Structural Changes

Lee

2021

Antioxidants

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Bacteria, like humans, face diverse kinds of stress during life. Oxidative stress, which is produced by cellular metabolism and environmental factors, can significantly damage cellular macromolecules, ultimately negatively affecting the normal growth of the cell. Therefore, bacteria have evolved a number of protective strategies to defend themselves and respond to imposed stress by changing the expression pattern of genes whose products are required to convert harmful oxidants into harmless products. Structural biology combined with biochemical studies has revealed the mechanisms by which various bacterial redox sensor proteins recognize the cellular redox state and transform chemical information into structural signals to regulate downstream signaling pathways.

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Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target

Cited by 35 publications

References 118 publications

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis

How Bacterial Redox Sensors Transmit Redox Signals via Structural Changes

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