The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model

EMBO Rep. 2006 Nov;7(11):1162-7. doi: 10.1038/sj.embor.7400826. Epub 2006 Oct 13.


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss and muscle wasting. In muscles of ALS patients, Nogo-A-a protein known to inhibit axon regeneration-is ectopically expressed at levels that correlate with the severity of the clinical symptoms. We now show that the genetic ablation of Nogo-A extends survival and reduces muscle denervation in a mouse model of ALS. In turn, overexpression of Nogo-A in wild-type muscle fibres leads to shrinkage of the postsynapse and retraction of the presynaptic motor ending. This suggests that the expression of Nogo-A occurring early in ALS skeletal muscle could cause repulsion and destabilization of the motor nerve terminals, and subsequent dying back of the axons and motor neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / chemically induced
  • Amyotrophic Lateral Sclerosis / therapy*
  • Animals
  • Disease Models, Animal*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Denervation*
  • Muscles / innervation
  • Muscles / metabolism*
  • Myelin Proteins / genetics
  • Myelin Proteins / metabolism*
  • Myelin Proteins / physiology
  • Neuromuscular Junction / physiopathology
  • Nogo Proteins
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1
  • Transfection


  • Myelin Proteins
  • Nogo Proteins
  • Rtn4 protein, mouse
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1