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.

SUBMITTER: Sasaki Y 

PROVIDER: S-EPMC5063586 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature