NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

Na Xie (1), Lu Zhang (2), Wei Gao (1), Canhua Huang (1,3), Peter Ernst Huber (4), Xiaobo Zhou (5), Changlong Li (6), Guobo Shen (2) and Bingwen Zou (1,4,7)

(1) State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China; (2) State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China; (3) School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China; (4) CCU Molecular and Radiation Oncology, German Cancer Research Center; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; (5) First Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (6) West China School of Basic Medical Sciences & Forensic Medicine, West China Hospital, Sichuan University, Chengdu 610041, China and (7) Department of Thoracic Oncology and Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Signal Transduction and Targeted Therapy (2020) 5:227

Published online: October 7, 2020 – www.nature.com/sigtrans
This article, published online by nature, says that:

  • “Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. …”  (bold added)
  • “…NAD+ and its metabolites function as a regulatory hub controlling a broad range of physiological processes, including redox homeostasis, genomic stability, gene expression, RNA processing, energy metabolism, immunity and inflammation, and circadian clock.…" (bold added)
  • “…Given the essential regulatory role of NAD+ in fundamental physiologies, NAD+ metabolic abnormalities contribute to the pathophysiology of various diseases, such as infection, cancers, metabolic diseases, aging and age-associated neurodegeneration disorders..." (bold added)
  • “NAD+ mitigates viral infection-induced oxidative damage..." (bold added)
  • “NAD+ contributes to the bactericidal activity.” (bold added)
  • “NAD+ deficiency accelerates aging.” (bold added)
  • “NAD+ ameliorates the oxidative damage during aging. There is a growing awareness that oxidative damage is an essential driver of age-related deterioration in cell function…” (bold added)
  • “NADH/NADPH is a powerful reduce source for buffering oxidative stress, thereby protecting cells/tissues from oxidative stress during aging…” (bold added)
  • “NAD+ also regulates oxidative stress in cellular senescence...” (bold added)
  • “NAD+ deficiency correlates with disturbed circadian clocks during aging. Besides mitigating the oxidative damage, NAD+ can extend lifespan by driving the circadian rhythms.” (bold added)
  • The critical role of NAD+ pool in tumorigenesis. NAD+ not only acts as a co-enzyme for metabolic redox reactions, but also functions as a co-substrate to modulate the activity of NAD+-consuming enzymes that govern the critical steps in tumorigenesis, including genome stability, metabolism, cell growth, cell death, redox homeostasis and immune response.” (bold added)
  • “Linkages between NAD+ depletion and neurodegenerative disorders…These neural pathologies can be rescued by NAD+ boosting.” (bold added)
  • NAD+ precursors can be used as a nutritional supplement to improve a broad spectrum of physiological functions and pathological processes… The therapeutic and preventive efficacy of NAD+ boosters, especially the soluble and orally bioavailable endogenous molecules NR [nicotinamide riboside], NAM [nicotinamide] and Niacin, have been assessed in a series of clinical trials in humans.” (bold added)
  • A healthy lifestyle and exercise are nonpharmacologic strategies to improve the body’s resilience and extend healthy lifespan through enhancing NAD+ levels. NAD+ boosters can be applied for a broad spectrum of NAD+ deficiency related pathologies, such as infection, cancer, metabolic diseases, acute injury, aging and aging-related neurodegenerative disorders..." (bold added)

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