dSarm/Sarm1 is required for activation of an injury-induced axon death pathway Academic Article uri icon

Overview

MeSH Major

  • Armadillo Domain Proteins
  • Axons
  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Neurons
  • Wallerian Degeneration

abstract

  • Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway.

publication date

  • July 27, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5225956

Digital Object Identifier (DOI)

  • 10.1126/science.1223899

PubMed ID

  • 22678360

Additional Document Info

start page

  • 481

end page

  • 4

volume

  • 337

number

  • 6093