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.
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.