Cel
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.
Dziedzina nauki
Słowa kluczowe
Temat(-y)
Zaproszenie do składania wniosków
FP7-PEOPLE-2007-2-1-IEF
Zobacz inne projekty w ramach tego zaproszenia
System finansowania
MC-IEF - Intra-European Fellowships (IEF)Koordynator
35037 Marburg
Niemcy