Document Type
Article
Publication Date
1-10-2019
Early Online Version
5-11-2018
JOURNAL
Antioxidants & Redox Signaling
VOLUME NUMBER
30
ISSUE NUMBER
2
PAGE NUMBERS
251-294
ISSN
1557-7716
Embargo Period
1-24-2020
ANZSRC / FoR Code
111716 Preventive Medicine| 111799 Public Health and Health Services not elsewhere classified
Reportable Items (HERDC/ERA)
C1
Abstract
Significance: Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that serves as an essential cofactor and substrate for a number of critical cellular processes involved in oxidative phosphorylation and ATP production, DNA repair, epigenetically modulated gene expression, intracellular calcium signaling, and immunological functions. NAD+ depletion may occur in response to either excessive DNA damage due to free radical or ultraviolet attack, resulting in significant poly(ADP-ribose) polymerase (PARP) activation and a high turnover and subsequent depletion of NAD+, and/or chronic immune activation and inflammatory cytokine production resulting in accelerated CD38 activity and decline in NAD+ levels. Recent studies have shown that enhancing NAD+ levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain. Therefore, promotion of intracellular NAD+ anabolism represents a promising therapeutic strategy for age-associated degenerative diseases in general, and is essential to the effective realization of multiple benefits of healthy sirtuin activity. The kynurenine pathway represents the de novo NAD+ synthesis pathway in mammalian cells. NAD+ can also be produced by the NAD+ salvage pathway.
Recent Advances: In this review, we describe and discuss recent insights regarding the efficacy and benefits of the NAD+ precursors, nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), in attenuating NAD+ decline in degenerative disease states and physiological aging.
Critical Issues: Results obtained in recent years have shown that NAD+ precursors can play important protective roles in several diseases. However, in some cases, these precursors may vary in their ability to enhance NAD+ synthesis via their location in the NAD+ anabolic pathway. Increased synthesis of NAD+ promotes protective cell responses, further demonstrating that NAD+ is a regulatory molecule associated with several biochemical pathways.
Future Directions: In the next few years, the refinement of personalized therapy for the use of NAD+ precursors and improved detection methodologies allowing the administration of specific NAD+ precursors in the context of patients' NAD+ levels will lead to a better understanding of the therapeutic role of NAD+ precursors in human diseases.
Link to publisher version (DOI)
https://doi.org/10.1089/ars.2017.7269
Recommended Citation
Braidy, N., Berg, J., Clement, J., Khorshidi, F., Poljak, A., ... Sachdev, P. (2019). Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes. Antioxidants & Redox Signaling, 30(2), 251-294. doi:10.1089/ars.2017.7269
Comments
Available for download is the accepted version of the following article: Braidy, N., Berg, J., Clement, J., Khorshidi, F., Poljak, A., ... Sachdev, P. (2018). Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes. Antioxidants & Redox Signaling, 30(2), 251-294, which has now been formally published in final form at Antioxidants & Redox Signaling at https://doi.org/10.1089/ars.2017.7269 This original submission version of the article may be used for non-commercial purposes in accordance with the Mary Ann Liebert, Inc., publishers’ self-archiving terms and conditions.