| First Author | Ezzi SA | Year | 2010 |
| Journal | J Neurochem | Volume | 115 |
| Issue | 5 | Pages | 1102-11 |
| PubMed ID | 20807312 | Mgi Jnum | J:168609 |
| Mgi Id | MGI:4889122 | Doi | 10.1111/j.1471-4159.2010.06979.x |
| Citation | Ezzi SA, et al. (2010) Neuronal over-expression of chromogranin A accelerates disease onset in a mouse model of ALS. J Neurochem 115(5):1102-11 |
| abstractText | 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. |
