Cel The hyper-phosphorylated microtubule-associated protein tau is the main component of aggregated proteins forming, intracellular paired helical filaments and neurofibrillary tangles in brain-patients with Alzheimer and apos;s disease (AD). On the other hand a-synuclein is the major component of Lewy bodies, inclusions in brain, the main feature of Parkinson and apos;s disease (PD). Several reports suggest overlap in pathology, since both are found in plaques (AD) and Lewy bodies (PD), and since co-expression of alpha synuclein and tau triggers enhanced neuro-degeneration in transgenic mice.In order to understand molecular mechanism of aggregation we will develop humanized yeast models to study aggregation of tau, a-synuclein and the combination. We already demonstrated that yeast recapitulates several aspects related to the pathogenesis of tau and a-synuclein in neuronal cells as in double transgenic mice. The aim of this project is the further development and the use of yeast models to unravel the molecular bas is of tau and a-synuclein aggregation and their interactions.The project consists of several activities:(1) Study the effect of tau and a-synuclein phosphorylation on aggregation and toxicity in yeast (analysis of tau epitopes in combination with over-expression or deletion of appropriate kinases and phosphatases)(2) Establish a toxicity matrix in which the effects are described for co-expression of different phosphorylation variants and mutants of both proteins.(3) Evaluate the correlation between prot easomal/autophagic proteolysis and aggregation (in vivo observation of proteolytic processes and comparison with toxicity triggered by aggregation of both proteins)(4)Identify novel proteins involved in amyloidogenesis (screening of a human hippocampus cD NA and yeast genomic DNA libraries) that enhance or reduce the toxicity of co-expression of tau and a-synuclein. Dziedzina nauki medical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicineneurologyparkinson Program(-y) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Temat(-y) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Zaproszenie do składania wniosków FP6-2002-MOBILITY-5 Zobacz inne projekty w ramach tego zaproszenia System finansowania EIF - Marie Curie actions-Intra-European Fellowships Koordynator KATHOLIEKE UNIVERSITEIT LEUVEN Wkład UE Brak danych Adres Oude Markt 13 LEUVEN Belgia Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych
