Objective Neurodegenerative disorders are an increasing healthcare problem. Many of these diseases are characterized by aggregation of proteins, which leads to neuronal dysregulation and cell death. Neurofibrillary tangles, pathological aggregates of tau protein, are the characteristic neuropathological stigmata defining a group of disorders termed Tauopathies. In Frontotemporal Dementias with Parkinsonism linked to Chromosome 17 (FTDP-17), mutations in the tau gene have been identified as cause of the disease. Mice expressing FTDP-17-mutant tau protein develop age-related accumulations of neurofibrillary tangles, behavioural impairments and neuronal cell loss, similar to patients with FTDP-17. When the expression of such mutant tau protein was suppressed by means of a tetracycline-controlled expression system in mice with advanced pathology, cognitive deficits were reversed and neuronal loss was prevented. We therefore propose to study if the small inference RNA (siRNA) technique can be instrumentalized in transgenic mice overexpressing human wild-type or mutant tau (R406/P301S) to suppress tau-gene expression, neuronal cell loss and behavioural deficits. To achieve widespread distribution of siRNA in the brain, a polyethyleneimine delivery system with intracerebroventricular administration will be used, which technique has a good chance to qualify for clinical application. We believe that this project will significantly advance the research in tau-related pathologies. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineneurologydementiamedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticschromosomes Keywords FTDP-17 Neurodegeneration Tau Tauopathies polyethyleneimine siRNA Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Call for proposal FP7-PEOPLE-2007-2-1-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator PHILIPPS UNIVERSITAET MARBURG Address Biegenstrasse 10 35037 Marburg Germany See on map Region Hessen Gießen Marburg-Biedenkopf Activity type Higher or Secondary Education Establishments Administrative Contact Günter U. Höglinger (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 158 694,85
