NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD<sup>+</sup> depletion.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27735788.
- Also identified by DOI 10.7554/eLife.19749 and PMC identifier 5063586.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Overexpression of the NAD<sup>+</sup> biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD<sup>+</sup> 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<sup>+</sup> metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD<sup>+</sup> synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD<sup>+</sup> consumption that is central to axon degeneration.
Medical subject headings
- Armadillo Domain Proteins
- Axons
- Cytoskeletal Proteins
- Nerve Degeneration
- Nicotinamide-Nucleotide Adenylyltransferase