A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus 英文参考文献.docVIP

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A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus 英文参考文献.doc

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A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus 英文参考文献

APeptideMimeticTargetingTrans-HomophilicNCAM BindingSitesPromotesSpatialLearningandNeural PlasticityintheHippocampus IgorKraev1.,ChristianHenneberger2.,ClaraRossetti3.,LisaConboy3.,LeneB.Kohler4 ,Martina Fantin3,AlistairJennings2,CesarVenero5,VictorPopov1,DmitriRusakov2,MichaelG.Stewart1*, ElisabethBock4,VladimirBerezin4,CarmenSandi3* 1Department of Life Sciences, The Open University, Milton Keynes, United Kingdom, 2Department of Clinical and Experimental Epilepsy, Institute of Neurology, UniversityCollegeLondon(UCL),London,UnitedKingdom,3LaboratoryofBehavioralGenetics,BrainMindInstitute,EPFL,Lausanne,Switzerland,4ProteinLaboratory, Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark, 5Department of Psychobiology, UNED, Ciudad Universitaria,Madrid,Spain Abstract Thekeyrolesplayedbytheneuralcelladhesionmolecule(NCAM)inplasticityandcognitionunderscorethismembrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of actions, which raise the question as to which NCAM fragment should be targeted. Synthetic NCAM mimetic peptides that mimic NCAM sequences relevant to specific interactions allow identification of the most promising targets within NCAM. Recently, adecapeptide ligand of NCAM— plannexin, which mimics a homophilictrans-binding site in Ig2 and binds to Ig3—was developed as a tool for studying NCAM’strans-interactions.Inthisstudy,weinvestigatedplannexin’sabilitytoaffectneuralplasticityandmemoryformation. We found that plannexin facilitates neurite outgrowth in primary hippocampal neuronal cultures and improves spatial learning in rats, both under basal conditions and under conditions involving a deficit in a key plasticity-promoting posttranslational modification of NCAM, its polysialylation. We also found that plannexin enhances excitatory synaptic transmissioninhippocampalareaCA1,