Objective Alzheimer’s disease (AD) and other dementias affect over 7 million individuals in Europe. There is, as yet, no treatment to halt or reverse disease progression despite huge investments into research. The accumulation of the amyloid beta-peptide (Abeta), derived from the amyloid precursor protein (APP) in the brain, is a key factor in the development of AD but the roles of other APP metabolites are poorly understood. This project will focus on one of these metabolites, its intracellular domain, AICD, and the mechanism for its nuclear trafficking and gene transcriptional regulation, especially of the Abeta-degrading enzyme, neprilysin (NEP), which maintains Abeta homeostasis. These studies will focus on the differential contributions of the three APP isoforms to AICD production, nuclear trafficking and gene regulation, and will use a variety of neuronal and non-neuronal models to analyse epigenetic changes mediating NEP expression including chromatin composition of the NEP gene in active and downregulated states and whether APP isoform effects are direct or indirect. In parallel, other putative AICD-responsive genes will be compared (aquaporin, GSK-3beta). This will allow us to formulate strategies for up-regulation of key neuroprotective genes in disease leading to potential new therapeutic approaches. The project will provide the Research Fellow with broad experience in molecular neuroscience (from bioimaging and protein trafficking to chromatin analysis and gene regulation) in a well-founded, integrated and multi-disciplinary environment for AD research. Fields of science medical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesbiological sciencesmolecular biologymolecular neurosciencenatural sciencesbiological sciencesgeneticsepigenetics 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) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2010-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator UNIVERSITY OF LEEDS Address Woodhouse lane LS2 9JT Leeds United Kingdom See on map Region Yorkshire and the Humber West Yorkshire Leeds Activity type Higher or Secondary Education Establishments Administrative Contact Martin Hamilton (Mr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
