Objective Excitotoxicity contributes significantly to neuronal cell death in a number of neurological conditions including stroke, head trauma, and Huntington's disease. The recent discovery of the proteins that anchor and interact with glutamate receptors opens for a new strategical approach to cytoprotective therapy. The present project aims at exploiting this conceptual advance to provide a platform for cytoprotective therapies that do not interfere unduly with synaptic transmission.Glutamate receptor interacting proteins (interactors) serve dual purpose. They determine the level and site of glutamate receptor expression within the cells and connect the receptors to specific intracellular signalling pathways. Both roles are interesting from a therapeutical perspective. Thus, excitotoxicity might be alleviated by modulation of the surface expression of glutamate receptors, as well as by interfering with their downstream signalling.The first part of the project aims at providing a more complete picture of the functional roles of interactors (WP1-3). It is envisaged that we will be able to identify novel interactors and that we will be in a position to understand, at a molecular level, how the different interactors connect with glutamate receptors and with each other. This part of the project will also elucidate the principles that govern the turnover and surface expression of glutamate receptors and the mechanisms that couple the individual receptors to specific downstream effectors of excitotoxicity.The second part (WP4 and 5) aims at exploiting the increased insight obtained through the first part of the project to design ways to alleviate excitotoxicity in different model systems. In designing these experiments the complex of glutamate receptor interacting proteins will be viewed as a 'nodal point' in orchestrating the surface expression of receptors and in activating appropriate and inappropriate (excitotoxic) signalling pathways. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineneurologystroke Keywords CREB glutamate receptors interacting proteins ischemia pro-survival genes Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2003-2.1.3-6 - Excitotoxic neuronal cell death Call for proposal FP6-2003-LIFESCIHEALTH-I See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator UNIVERSITY OF OSLO EU contribution No data Address Problemveien 57 1073 OSLO Norway See on map Links Website Opens in new window Total cost No data Participants (7) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITY OF BRISTOL United Kingdom EU contribution No data Address Senate House, Tyndall Avenue BRISTOL See on map Links Website Opens in new window Total cost No data NEUROSEARCH A/S Denmark EU contribution No data Address Pederstrupvej 93 BALLERUP See on map Links Website Opens in new window Total cost No data INSTYTUT BIOLOGII DOSWIADCZALNEJ IM. M. NENCKIEGO PAN Poland EU contribution No data Address Pasteura 3 WARSAW See on map Links Website Opens in new window Total cost No data RUPRECHT-KARLS-UNIVERSITÄT HEIDELBERG Germany EU contribution No data Address Seminarstr. 2 HEIDELBERG See on map Links Website Opens in new window Total cost No data FLUOFARMA SA France EU contribution No data Address 2, Rue Robert Escarpit PESSAC See on map Links Website Opens in new window Total cost No data UNIVERSITY OF SOUTHERN DENMARK Denmark EU contribution No data Address Campusvej 55 ODENSE M See on map Links Website Opens in new window Total cost No data CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE France EU contribution No data Address 3 rue Michel Ange PARIS See on map Links Website Opens in new window Total cost No data