NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+depletion

Abstract

Overexpression of the NAD+biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+synthesis, NMNAT1 instead blocks the injury-induced, SARM1- dependent NAD+consumption that is central to axon degeneration.