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Epigenetic regulation of Alzheimer's disease related genes

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.

Call for proposal

FP7-PEOPLE-2010-IEF
See other projects for this call

Coordinator

UNIVERSITY OF LEEDS
Address
Woodhouse Lane
LS2 9JT Leeds
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 101 274,80
Administrative Contact
Martin Hamilton (Mr.)