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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

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

Sasaki Yo Y Nakagawa Takashi T Mao Xianrong X DiAntonio Aaron A Milbrandt Jeffrey J

eLife 20161013

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-depe ...[more]

PMID: 27735788

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