Objectif Inhibitory chondroitin sulphate proteoglycans (CSPGs) have several roles in CNS damage and repair, revealed by their digestion with chondroitinase. Most recently, digestion of CSPGs in the limbic system and cortex has led to a very substantial enhancement of memory.The effects of CSPGs on plasticity and memory are largely through their concentration into PNNs, because transgenics lacking the PNN component link protein in the CNS have very attenuated PNNs, and show continuing plasticity into adulthood, and enhanced memory in just the same way as chondroitinase-treated animals. The PNN is therefore a novel therapeutic target that has not been explored.This application focuses particularly on enhancement of memory through manipulation of PNNs.In Alzheimer’s disease (AD) and ageing the main cognitive disability is loss of memory. The enhancement of memory following chondroitinase treatment or PNN knockout in object memory is many times greater than obtained using cholinesterase inhibitors (the only currently available treatment for memory enhancement). PNN manipulation is therefore a particularly promising avenue for developing treatments to overcome the main cognitive disability of AD and ageing.The aims of the application are:1. Test the extent of memory enhancement due to PNN manipulation in models of AD due to Abeta, tau mutations and in aged CNS.2. Establish the molecular mechanism for PNN effects on memory, focusing on Semaphorin3 presentation by PNNs, and direct effects via the PTPsigma receptor.3. Discover the sulphation modifications of the CSPG glycan chains that enable binding of Semaphorin3s, activation of the PTPsigma receptor.4. Analyse molecules that bind to PNN glycans, to identify new potential effectors of PNN effects on memory and plasticity5. Testing in memory and plasticity models of novel PNN-targeted approaches. Champ scientifique medical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS5 - ERC Advanced Grant - Neurosciences and neural disorders Appel à propositions ERC-2011-ADG_20110310 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contribution de l’UE € 2 450 543,00 Adresse TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Royaume-Uni Voir sur la carte Région East of England East Anglia Cambridgeshire CC Type d’activité Higher or Secondary Education Establishments Contact administratif Renata Schaeffer (Ms.) Chercheur principal James Fawcett (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Royaume-Uni Contribution de l’UE € 2 450 543,00 Adresse TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Voir sur la carte Région East of England East Anglia Cambridgeshire CC Type d’activité Higher or Secondary Education Establishments Contact administratif Renata Schaeffer (Ms.) Chercheur principal James Fawcett (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
