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Elife. 2016 Oct 13;5. pii: e19749. doi: 10.7554/eLife.19749.

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

Author information

1
Department of Genetics, Washington University School of Medicine, Saint Louis, United States.
2
Frontier Research Core for Life Sciences, University of Toyama, Toyama, Japan.
3
Department of Developmental Biology, Washington University School of Medicine, Saint Louis, United States.

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.

KEYWORDS:

NAD; Nampt; Nmnat; SARM1; Wlds; axonal degeneration; mouse; neuroscience

PMID:
27735788
PMCID:
PMC5063586
DOI:
10.7554/eLife.19749
[Indexed for MEDLINE]
Free PMC Article

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