P0 GLYCOPROTEIN TRAFFICKING AND QUALITY CONTROL IN CHARCOT MARIE TOOTH 1B NEUROPATHY

Hereditary neuropathies are a common problem seen in Neurology Clinics, in which the wrapping around nerves that conduct impulses to muscles are damaged. Many neuropathies appear in every generation of a stricken family and unfortunately affect children. Although disease genes have been identified for neuropathies, how disease is caused is unknown and there is no effective treatment. Genetic studies of hereditary neuropathies strongly suggest that most do not result simply because the disease gene does not work. Instead the disease gene probably has a ‘toxic’ effect on the cells in the nerve. In order to understand that toxicity, we will study mice containing the mutant genes, that we have already shown produce excellent models of hereditary neuropathies; they become weak and have difficulty walking over time. When examined under the microscope, their nerves resemble those of human patients. In some of the more severely affected mice, we have found activation of a pathway that could be toxic to the cells in nerve. In this study, we propose to further study the activation of this pathway, and how its activation may worsen nerve function, in order to identify potential ‘targets’ for new drugs that could treat hereditary neuropathies.