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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Armadillo Domain Proteins / genetics*
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Armadillo Domain Proteins / metabolism
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Axons / metabolism*
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Axons / pathology
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Cytoskeletal Proteins / genetics*
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Cytoskeletal Proteins / metabolism
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Ganglia, Spinal / metabolism
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Ganglia, Spinal / pathology
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Mice
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NAD / metabolism
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Nerve Degeneration / genetics*
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Nerve Degeneration / pathology
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Nicotinamide-Nucleotide Adenylyltransferase / genetics*
Substances
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Armadillo Domain Proteins
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Cytoskeletal Proteins
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SARM1 protein, mouse
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NAD
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Nicotinamide-Nucleotide Adenylyltransferase
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Nmnat1 protein, mouse