Objective Amyloid precursor protein (APP) is genetically and biochemically linked to the pathogenesis of Alzheimer¿s disease (AD), the most common cause of senile dementia in industrialized countries. It has been proposed that reduction of the level or activity of c ertain APP fragments, in addition to accumulation of Abeta peptide, may play a critical role in the cognitive dysfunction associated with AD. To test this hypothesis, it is important to understand the roles that full-length APP and its fragments normally p lay in neuronal structure and function. Emerging evidence suggests that sAPP, the secreted N-terminal fragment of APP, can be considered as a signaling polypeptide that evokes coordinated responses in neuronal and some non-neuronal target cells. Prerequisi te for such functions is the existence of a membrane receptor for sAPP, which has been postulated but is at present unidentified. The aim of the proposed study is to identify sAPP receptors and characterize them biochemically. For this purpose, binding stu dies with recombinant sAPP will be performed with sections of brain and other tissues. In addition, the results of the tissue-binding approach will be confirmed by conducting binding studies with cultured cells. To be able to analyze the complex of sAPP wi th its receptor, the complex will be covalently linked via the photocrosslinking amino acid p-benzoyl-L.phenylalanine. Introduction of the photolabile amino acid at defined positions ensures that only direct binding partners are stably bound. Thereafter, t he complex will be purified and sAPP-bound proteins will be characterized by mass-spectrometrical methods. Fields of science medical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencesorganic chemistryamines Programme(s) 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 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2002-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator FLANDERS INTERUNIVERSITY INSTITUTE FOR BIOTECHNOLOGY VZW Address Rijvisschestraat 120 Zwijnaarde Belgium See on map Links Website Opens in new window EU contribution No data
