Boosting NAD+ Production Protects Nerves and Slows Axon Degeneration After Injury: Preclinical Findings

Synopsis

Axonal degeneration, a major cause of nerve damage in neurodegenerative diseases and after traumatic injury, is a self-destructive process separate from normal cell death. Previous studies showed that increasing levels of the enzyme Nmnat1 or adding nicotinamide adenine dinucleotide (NAD+) can protect neurons from degeneration. Since NAD+ can be made in cells through several different biochemical routes, this study tested whether other enzymes and precursors involved in these NAD+ biosynthetic pathways could also slow down axonal breakdown. The researchers found that boosting NAD+ production in various ways—by overexpressing specific enzymes or adding NAD+ precursors—helped preserve axons after injury. Nmnat1 provided the strongest protection, while other enzymes such as nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase also offered moderate benefits when their respective substrates were present. Interestingly, the location of NAD+ production within the cell did not affect its protective effect, as both mitochondrial and cytoplasmic forms were effective. These findings suggest that enhancing NAD+ biosynthesis through different pathways could be a promising strategy to prevent or delay axonal degeneration in neurological disorders or nerve injuries.

Journal

Journal of Neuroscience