Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism

Neuron. 2016 Feb 3;89(3):449-60. doi: 10.1016/j.neuron.2015.12.023.


Wallerian axon degeneration is a form of programmed subcellular death that promotes axon breakdown in disease and injury. Active degeneration requires SARM1 and MAP kinases, including DLK, while the NAD+ synthetic enzyme NMNAT2 prevents degeneration. New studies reveal that these pathways cooperate in a locally mediated axon destruction program, with NAD+ metabolism playing a central role. Here, we review the biology of Wallerian-type axon degeneration and discuss the most recent findings, with special emphasis on critical signaling events and their potential as therapeutic targets for axonopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Armadillo Domain Proteins / metabolism*
  • Axons / metabolism*
  • Axons / pathology*
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism*
  • NAD / metabolism*
  • Neuroprotective Agents / metabolism*
  • Nicotinamide-Nucleotide Adenylyltransferase / metabolism
  • Signal Transduction*
  • Wallerian Degeneration / metabolism*
  • Wallerian Degeneration / pathology


  • Armadillo Domain Proteins
  • Cytoskeletal Proteins
  • Neuroprotective Agents
  • SARM1 protein, mouse
  • NAD
  • Mitogen-Activated Protein Kinases
  • Nicotinamide-Nucleotide Adenylyltransferase
  • Nmnat2 protein, mouse