Objetivo
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.
Ámbito científico (EuroSciVoc)
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
- ciencias naturalesciencias biológicasneurobiología
- ciencias médicas y de la saludmedicina básicaneurologíademenciaalzheimer
- ciencias médicas y de la saludmedicina básicafisiologíahomeostasis
- ciencias naturalesciencias biológicasbioquímicabiomoléculasproteínasenzima
- ciencias naturalesciencias biológicasbiología molecularneurociencia molecular
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Tema(s)
Convocatoria de propuestas
FP7-PEOPLE-2010-IEF
Consulte otros proyectos de esta convocatoria
Régimen de financiación
MC-IEF - Intra-European Fellowships (IEF)Coordinador
LS2 9JT Leeds
Reino Unido