Role of NADþ in regulating cellular and metabolic signaling pathways

Authors

• Sara Amjad, Shibli National College, Azamgarh, Uttar Pradesh, India
• Sabah Nisar, Functional and Molecular Imaging Laboratory, Cancer Research Department, Sidra Medicine, Doha, Qatar
• Ajaz A. Bhat, Functional and Molecular Imaging Laboratory, Cancer Research Department, Sidra Medicine, Doha, Qatar
• Ab Rauf Shah, University of Nebraska-LincolnFollow
• Michael P. Frenneaux, Academic Health System, Hamad Medical Corporation, Doha, Qatar
• Khalid Fakhro, Department of Human Genetics, Sidra Medicine, Doha, Qatar
• Mohammad Haris, Functional and Molecular Imaging Laboratory, Cancer Research Department, Sidra Medicine, Doha, Qatar
• Ravinder Reddy, 8 Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
• Zoltan Patay, Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN, USA
• Joseph Baur, 0Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA, USA
• Puneet Bagga, Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN, USA

Document Type

Article

Date of this Version

2-17-2021

Comments

CC-BY

Abstract

Background: Nicotinamide adenine dinucleotide (NAD⁺), a critical coenzyme present in every living cell, is involved in a myriad of metabolic processes associated with cellular bioenergetics. For this reason, NAD⁺ is often studied in the context of aging, cancer, and neurodegenerative and metabolic disorders.

Scope of review: Cellular NAD⁺ depletion is associated with compromised adaptive cellular stress responses, impaired neuronal plasticity, impaired DNA repair, and cellular senescence. Increasing evidence has shown the efficacy of boosting NAD⁺ levels using NAD⁺ precursors in various diseases. This review provides a comprehensive understanding into the role of NAD⁺ in aging and other pathologies and discusses potential therapeutic targets.

Major conclusions: An alteration in the NAD⁺/NADH ratio or the NAD⁺ pool size can lead to derailment of the biological system and contribute to various neurodegenerative disorders, aging, and tumorigenesis. Due to the varied distribution of NAD⁺/NADH in different locations within cells, the direct role of impaired NAD⁺-dependent processes in humans remains unestablished. In this regard, longitudinal studies are needed to quantify NAD⁺ and its related metabolites. Future research should focus on measuring the fluxes through pathways associated with NAD⁺synthesis and degradation.

Background: Nicotinamide adenine dinucleotide (NAD⁺), a critical coenzyme present in every living cell, is involved in a myriad of metabolic processes associated with cellular bioenergetics. For this reason, NAD⁺ is often studied in the context of aging, cancer, and neurodegenerative and metabolic disorders.

Scope of review: Cellular NAD⁺ depletion is associated with compromised adaptive cellular stress responses, impaired neuronal plasticity, impaired DNA repair, and cellular senescence. Increasing evidence has shown the efficacy of boosting NAD⁺ levels using NAD⁺ precursors in various diseases. This review provides a comprehensive understanding into the role of NAD⁺ in aging and other pathologies and discusses potential therapeutic targets.

Major conclusions: An alteration in the NAD⁺/NADH ratio or the NAD⁺ pool size can lead to derailment of the biological system and contribute to various neurodegenerative disorders, aging, and tumorigenesis. Due to the varied distribution of NAD⁺/NADH in different locations within cells, the direct role of impaired NAD⁺-dependent processes in humans remains unestablished. In this regard, longitudinal studies are needed to quantify NAD⁺ and its related metabolites. Future research should focus on measuring the fluxes through pathways associated with NAD⁺ synthesis and degradation.