Benefits of Enhancing Nicotinamide Adenine Dinucleotide Levels in Damaged or Diseased Nerve Cells.

Abstract

Three unbiased lines of research have commonly pointed to the benefits of enhanced levels of nicotinamide adenine dinucleotide (NAD⁺) to diseased or damaged neurons. Mice carrying a triplication of the gene encoding the culminating enzyme in NAD⁺ salvage from nicotinamide, NMNAT, are protected from a variety of insults to axons. Protection from Wallerian degeneration of axons is also observed in flies and mice bearing inactivating mutations in the SARM1 gene. Functional studies of the SARM1 gene product have revealed the presence of an enzymatic activity directed toward the hydrolysis of NAD⁺ Finally, an unbiased drug screen performed in living mice led to the discovery of a neuroprotective chemical designated P7C3. Biochemical studies of the P7C3 chemical show that it can enhance recovery of NAD⁺ from nicotinamide by activating NAMPT, the first enzyme in the salvage pathway. In combination, these three unrelated research endeavors offer evidence of the benefits of enhanced NAD⁺ levels to damaged neurons.