NeuroSys - Systems Biology of the Disturbed Neuron-Glia Network in Neuropathies

The molecular defects underlying hereditary neuropathies (Charcot-Marie-Tooth disease, CMT) are known and it is evident that very different subcellular defects in glial and neuronal cells cause axonal loss, which marks the ‘final common pathway’ of all neuropathies, including the acquired (e.g. diabetic) subtypes. However, the molecular mechanisms of axonal degeneration and neuronal loss, which ultimately lead to the clinical manifestations, are poorly understood and there is no treatment option available, neither for hereditary nor diabetic neuropathies. In the combined academic and industrial systems biological approach proposed here, we aim to make use of available data-sets obtained with the molecularly well defined transgenic CMT animal models and sophisticated in-depth bioinformatic and mathematical analyses (i) to generate a model of the disturbed neuron-glia interactions in CMT, (ii) to identify and validate novel targets, mechanisms and potential diagnostic biomarkers for hereditary and diabetic neuropathies, (iii) to rationally design novel pre-clinical therapeutic approaches and (iv) to transfer experimental treatment protocols to patients.