Importance:
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, gene expression epigenetically modulated intracellular calcium signalling and immunology. functions NAD+ depletion can occur in response to excessive DNA damage due to ultraviolet or free radical attack, resulting in significant activation of poly(ADP-ribose) polymerase (PARP) and high turnover and subsequent NAD+ depletion, and/or chronic immune activation and inflammatory cytokine production resulting in accelerated CD38 activity and decreased NAD+ levels.
Recent studies have shown that enhancing NAD+ levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain. Therefore, the promotion of intracellular NAD+ anabolism represents a promising therapeutic strategy for age-associated degenerative diseases in general and is essential for the effective realization of the multiple benefits of healthy sirtuin activity. The kynurenine pathway represents the de novo NAD+ synthesis pathway in mammalian cells. NAD+ can also be produced via the NAD+ salvage pathway.
Recent Advances:
In this review, we describe and discuss recent insights into the efficacy and benefits of the NAD+ precursors, nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), for attenuate NAD+. decrease in degenerative disease states and physiological ageing.
Critical issues:
Results obtained in recent years have shown that NAD+ precursors can play important protective roles in various diseases. However, in some cases, these precursors may vary in their ability to enhance NAD+ synthesis through their location in the NAD+ anabolic pathway. Increased NAD+ synthesis promotes protective cellular responses, further demonstrating that NAD+ is a regulatory molecule associated with several biochemical pathways.
Future Directions:
In the coming years, refinement of personalized therapy for the use of NAD+ precursors and improved screening methodologies that allow delivery 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.
Keywords:
NAD+, nicotinamide, sirtuins, oxidative stress, DNA damage