NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion
Y Sasaki, T Nakagawa, X Mao, A DiAntonio… - elife, 2016 - elifesciences.org
elife, 2016•elifesciences.org
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. DOI: http://dx …
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. DOI: http://dx …
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.
DOI: http://dx.doi.org/10.7554/eLife.19749.001
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