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

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.