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  3. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

  • Signal Transduct Target Ther. 2020 Oct 7;5(1):227. doi: 10.1038/s41392-020-00311-7.
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 7,  Bingwen Zou 8 9 10
Affiliations

Affiliations

  • 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. changlongli@scu.edu.cn.
  • 7 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China. shenguobo@126.com.
  • 8 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. zoubingwen81@163.com.
  • 9 CCU Molecular and Radiation Oncology, German Cancer Research Center; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. zoubingwen81@163.com.
  • 10 Department of Thoracic Oncology and Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. zoubingwen81@163.com.
  • # Contributed equally.
PMID: 33028824 DOI: 10.1038/s41392-020-00311-7
Abstract

Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, Infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as Enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent Enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, Cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

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