Neuronal over-expression of chromogranin A accelerates disease onset in a mouse model of ALS

J Neurochem. 2010 Dec;115(5):1102-11. doi: 10.1111/j.1471-4159.2010.06979.x. Epub 2010 Oct 26.


Recent studies provided evidence that chromogranins can interact with mutant superoxide dismutase 1 (SOD1) and that chromogranin B (CgB) may act as a susceptibility gene and modifier of onset in amyotrophic lateral sclerosis (ALS). To further investigate the role of chromogranins in ALS pathogenesis, we generated SOD1(G37R) mice that over-express CgA under the control of Thy1 promoter. Here, we report that neuronal over-expression of CgA in SOD1(G37R) mice caused acceleration of onset of motor impairment and exacerbation of motor neuron degeneration. The use of monoclonal antibody specific to misfolded mutant SOD1 demonstrated a higher level of misfolded SOD1 species in double transgenic mice compared to SOD1(G37R) mice, suggesting a stabilization of pathogenic SOD1 species by excess CgA. These results suggest a role of chromogranins as modulators of disease onset in ALS pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Cell Survival
  • Chromogranin A / genetics
  • Chromogranin A / metabolism*
  • Disease Models, Animal*
  • Female
  • Gene Expression Regulation / genetics*
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Immunoprecipitation / methods
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / metabolism*
  • Motor Neurons / pathology
  • Mutation / genetics
  • Nerve Degeneration / etiology
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Neuromuscular Junction / pathology
  • Protein Folding
  • Spinal Cord / pathology*
  • Superoxide Dismutase / genetics
  • Thy-1 Antigens / genetics


  • Chromogranin A
  • Glial Fibrillary Acidic Protein
  • Thy-1 Antigens
  • SOD1 G37R protein, mouse
  • Superoxide Dismutase