Abstract
Mutations in the Endosomal Sorting Complex Required for Transport-III gene, CHMP2B, have been identified as causing forms of frontotemporal dementia . Whilst this machinery operates to regulate lysosomal cargo sorting upon endosomes, new roles in repairing damaged nuclear and plasma membranes have recently emerged. We will utilise a multi-disciplinary approach encompassing neurobiology, cell biology and biophysics to test the hypothesis that disease-causing mutations in CHMP2B interfere with membrane repair and compromise cellular compartmentalisation. We think this may be a new way in which neuronal function is perturbed during neurodegenerative disease and could lead to novel therapies for these disorders.
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