Promoting NAD+ Metabolism: A new Target for Treating Degenerative Disease

Abstract

NAD+ is found in every cell of the body and is essential for life. It serves as a cofactor for dehydrogenase, reductase and hydroxylase enzymes where it facilitates electron transfer in major metabolic pathways such as glycolysis, the triacarboxylic acid (TCA) cycle, fatty acid synthesis and steroid hormone synthesis, enabling the conversion of the food we eat into the energy and chemical products the body needs. More recently it has been found that NAD+ is also required as a substrate by enzymes that regulate the expression of genes involved in cell viability and aging and in repair of damaged DNA. Through these reactions, NAD+ influences a variety of cell processes involved in cell health, including improving mitochondrial efficiency, enhancing cell viability, down-regulating inflammation, increasing the antioxidant capacity of cells and tissues, and activating the ‘longevity’ enzyme SIRT1. An increasing body of evidence indicates that enhancing NAD+ availability in the brain has the potential to moderate elements of the neurodegenerative disease processes associated with oxidative stress and aging, including Alzheimer’s disease. However there are difficulties associated with raising NAD+ levels using the classical pathway and vitamin B3 precursors nicotinic acid and nicotinamide. The recent discovery of two alternative naturally occurring B3 vitamins; nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) may resolve these problems. NR in particular has shown good efficacy in its ability to raise NAD+ levels under a variety of conditions. Directly boosting [NAD+] may present a new and exciting approach to preventing the natural decline in cellular energy and function as we age, particularly in the brain.