title: 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.
authors.affiliation: Department of Genetics, Washington University School of Medicine, Saint Louis, United States.
authors.forename: Yo
authors.identifier: 0000-0003-0024-0031
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Frontier Research Core for Life Sciences, University of Toyama, Toyama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Genetics, Washington University School of Medicine, Saint Louis, United States.
authors.forename: Xianrong
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, Saint Louis, United States.
authors.forename: Aaron
authors.identifier: 0000-0002-7262-0968
authors.initials: A
authors.lastname: DiAntonio
authors.affiliation: Department of Genetics, Washington University School of Medicine, Saint Louis, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics* / Q000378:metabolism; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009243:NAD / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics*
chemical_list: D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; C543961:SARM1 protein, mouse; D009243:NAD; D009612:Nicotinamide-Nucleotide Adenylyltransferase; C510972:Nmnat1 protein, mouse
keywords: NAD; Nampt; Nmnat; SARM1; Wlds; axonal degeneration; mouse; neuroscience