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

Abstract

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.

• Authors: Samer Abou Ezzi, Roxanne Larivière, Makoto Urushitani, Jean-Pierre Julien
• Journal: Journal of neurochemistry (J Neurochem) Vol. 115 Issue 5 Pg. 1102-11 (Dec 2010) ISSN: 1471-4159 [Electronic] England
• PMID: 20807312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.

Chemical References

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

Topics

• Amyotrophic Lateral Sclerosis (genetics, pathology, physiopathology)
• Animals
• Cell Survival
• Chromogranin A (genetics, 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, pathology)
• Mutation (genetics)
• Nerve Degeneration (etiology, metabolism, pathology)
• Neuromuscular Junction (pathology)
• Protein Folding
• Spinal Cord (pathology)
• Superoxide Dismutase (genetics)
• Thy-1 Antigens (genetics)