Pathogenesis of two axonopathies does not require axonal neurofilaments

Nature. 1998 Feb 5;391(6667):584-7. doi: 10.1038/35378.


Neurofilaments are a major component of the axonal cytoskeleton and their abnormal accumulation is a prominent feature of the cytopathology encountered in several neurodegenerative diseases. Thus, an attractive and widely held model of pathogenesis involves the participation of disrupted neurofilaments as a common toxic intermediate. Here, in direct contrast to this hypothesis, we show that two neurodegenerative disease models in the mouse, dystonia musculorum (dt) and a superoxide dismutase 1 (SOD1)-mediated form of human motor neuron disease (amyotrophic lateral sclerosis, ALS), progress with little or no abatement on a transgenic background in which neurofilaments are withheld from the axonal compartment. By specifically excluding a necessary role for axonal neurofilaments, our observations redefine the components of the pathogenic pathway leading to axon disruption in these two degenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / ultrastructure*
  • Amyotrophic Lateral Sclerosis / etiology*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Autoantigens / genetics
  • Axons / ultrastructure*
  • Carrier Proteins*
  • Collagen*
  • Cytoskeletal Proteins*
  • Dystonia Musculorum Deformans / etiology*
  • Dystonia Musculorum Deformans / pathology
  • Dystonin
  • Ganglia, Spinal / ultrastructure
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins*
  • Neurofilament Proteins / genetics
  • Non-Fibrillar Collagens*
  • Recombinant Fusion Proteins / genetics


  • Autoantigens
  • Carrier Proteins
  • Cytoskeletal Proteins
  • DST protein, human
  • Dst protein, mouse
  • Dystonin
  • Nerve Tissue Proteins
  • Neurofilament Proteins
  • Non-Fibrillar Collagens
  • Recombinant Fusion Proteins
  • collagen type XVII
  • neurofilament protein H
  • Collagen