2020
Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging
Sadasivam P, Fang XT, Toyonaga T, Lee S, Xu Y, Zheng MQ, Spurrier J, Huang Y, Strittmatter SM, Carson RE, Cai Z. Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular Imaging And Biology 2020, 23: 372-381. PMID: 33258040, PMCID: PMC8105262, DOI: 10.1007/s11307-020-01567-9.Peer-Reviewed Original ResearchConceptsBrain stemAlzheimer's diseaseMin postinjectionAnimal modelsAPP/PS1 miceReference regionStandardized uptake value ratioDynamic PET imaging dataUptake value ratioRodent brain tissueStatic PET scansDifferent imaging windowsPET imaging dataWild-type controlsReference tissue modelPS1 miceAD pathogenesisTherapeutic effectMouse modelRodent modelsLittermate controlsPET scansRodent brainPreclinical imaging studiesTherapeutic drug efficacy
2018
Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers
Kostylev MA, Tuttle MD, Lee S, Klein LE, Takahashi H, Cox TO, Gunther EC, Zilm KW, Strittmatter SM. Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers. Molecular Cell 2018, 72: 426-443.e12. PMID: 30401430, PMCID: PMC6226277, DOI: 10.1016/j.molcel.2018.10.009.Peer-Reviewed Original ResearchConceptsAmino-terminal GlyCellular prion proteinProtein phase separationAmyloid-β OligomersPlasma membraneMembraneless organellesAla residuesRecombinant PrPPrion proteinCell surfaceConformation shiftConformational transitionHelical conformationAβ speciesPrPSupSpongiform degenerationEndogenous AβOsOrganellesPrPCSuch domainsSpeciesDomainProteinAβOs
2017
Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes
Haas LT, Salazar SV, Smith LM, Zhao HR, Cox TO, Herber CS, Degnan AP, Balakrishnan A, Macor JE, Albright CF, Strittmatter SM. Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes. Cell Reports 2017, 20: 76-88. PMID: 28683325, PMCID: PMC5547898, DOI: 10.1016/j.celrep.2017.06.023.Peer-Reviewed Original ResearchConceptsAD transgenic mouse modelDisease pathologyMetabotropic glutamate receptor 5Allosteric modulationGlutamate receptor 5Alzheimer's disease pathologyTransgenic mouse brainSilent allosteric modulatorsTransgenic mouse modelBroad therapeutic windowMouse phenotypeAD interventionSynaptic depletionBrain slicesGlutamate signalingMouse modelTherapeutic windowAD phenotypeReceptor 5Mouse brainAllosteric modulatorsMemory deficitsCellular prion proteinPathological roleMGluR5Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
Fink KL, López-Giráldez F, Kim IJ, Strittmatter SM, Cafferty WB. Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury. Cell Reports 2017, 18: 2687-2701. PMID: 28297672, PMCID: PMC5389739, DOI: 10.1016/j.celrep.2017.02.058.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCentral nervous systemFunctional recoveryIntact neuronsAdult mammalian central nervous systemPartial spinal cord injuryInjury-induced sproutingUnilateral brainstem lesionsGreater functional recoverySpontaneous functional recoveryCorticospinal motor neuronsCorticospinal tract axonsMammalian central nervous systemWild-type miceNew synapse formationGrowth modulatorsAdjacent injuryBrainstem lesionsCord injuryFunctional deficitsIntact circuitryCNS neuronsMotor neuronsCircuit plasticityNervous system
2016
Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity
Smith LM, Strittmatter SM. Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity. Cold Spring Harbor Perspectives In Medicine 2016, 7: a024075. PMID: 27940601, PMCID: PMC5411685, DOI: 10.1101/cshperspect.a024075.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAβ oligomersSoluble Aβ oligomersFibrillary amyloidNeuronal impairmentSynaptic dysfunctionAD pathogenesisSynaptic toxicityAmyloid-β OligomersCellular prion proteinNeuronal cascadesFurther studiesCell surface proteinsDiseaseAβPrion proteinOligomer toxicityToxicityDysfunctionMolecular basisPathogenesisDementiaProteinPlaquesImpairmentCellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease
Salazar SV, Strittmatter SM. Cellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease. Biochemical And Biophysical Research Communications 2016, 483: 1143-1147. PMID: 27639648, PMCID: PMC5303667, DOI: 10.1016/j.bbrc.2016.09.062.Peer-Reviewed Original ResearchConceptsCellular prion proteinPrion proteinSignal transduction downstreamDisease pathophysiologyNeuronal surfaceMetabotropic glutamate receptor 5Neuronal cell surface moleculesGlutamate receptor 5Disease-associated stateAlzheimer's disease pathophysiologyAltered signal transductionTransduction downstreamSignal transductionGenetic evidenceSpecificity of bindingPyk2 kinaseCell surface moleculesFyn kinaseSynaptic dysfunctionAβO toxicitySynaptic transmissionMouse modelIntervention sitesReceptor 5Alzheimer's disease
2015
Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease
Haas LT, Salazar SV, Kostylev MA, Um JW, Kaufman AC, Strittmatter SM. Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease. Brain 2015, 139: 526-546. PMID: 26667279, PMCID: PMC4840505, DOI: 10.1093/brain/awv356.Peer-Reviewed Original ResearchConceptsCellular prion proteinDisease-related phenotypesPrion proteinMetabotropic glutamate receptor 5Glutamate receptor 5Protein tyrosine kinase 2 betaCalmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IIProtein kinase IIReceptor 5Protein associatesGenetic interactionsObligate complexesGenetic couplingDisease pathogenesisDisease pathologyKinase IIIntracellular proteinsAlzheimer's disease-related phenotypesSingle heterozygotesProteinBiochemical evidenceProtein mediatorsDisease-modifying interventionsTransgenic model mice
2014
Therapeutic Molecules and Endogenous Ligands Regulate the Interaction between Brain Cellular Prion Protein (PrPC) and Metabotropic Glutamate Receptor 5 (mGluR5)*
Haas LT, Kostylev MA, Strittmatter SM. Therapeutic Molecules and Endogenous Ligands Regulate the Interaction between Brain Cellular Prion Protein (PrPC) and Metabotropic Glutamate Receptor 5 (mGluR5)*. Journal Of Biological Chemistry 2014, 289: 28460-28477. PMID: 25148681, PMCID: PMC4192497, DOI: 10.1074/jbc.m114.584342.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsAntibodiesBinding SitesBiological AssayBrain ChemistryCell MembraneDisease Models, AnimalGene Expression RegulationHEK293 CellsHumansLigandsMiceMice, TransgenicPeptide MappingProtein BindingProtein Structure, TertiaryPrPC ProteinsReceptor, Metabotropic Glutamate 5Recombinant ProteinsSignal TransductionSmall Molecule LibrariesConceptsMetabotropic glutamate receptor 5Glutamate receptor 5Receptor 5Endogenous ligandMouse brainAD transgenic model miceCellular prion proteinAmino acids 91Transgenic model miceSoluble amyloid β (Aβ) oligomersAlzheimer's disease pathophysiologySilent allosteric modulatorsAgonists/antagonistsExtracellular AβOsMGluR5 activitySynthetic AβOsPrion proteinAmyloid-β OligomersModel miceCell membrane preparationsMGluR5Neurotoxic signalsBrain homogenatesAlzheimer's diseaseDisease pathophysiology
2012
Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons
Um JW, Nygaard HB, Heiss JK, Kostylev MA, Stagi M, Vortmeyer A, Wisniewski T, Gunther EC, Strittmatter SM. Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nature Neuroscience 2012, 15: 1227-1235. PMID: 22820466, PMCID: PMC3431439, DOI: 10.1038/nn.3178.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBlotting, WesternCalcium SignalingCell LineDendritic SpinesElectroencephalographyEnzyme ActivationHumansMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNeuronsPhosphorylationProtein BindingProto-Oncogene Proteins c-fynPrPC ProteinsRatsReceptors, N-Methyl-D-AspartateSeizuresSynapses
2011
Cartilage Acidic Protein–1B (LOTUS), an Endogenous Nogo Receptor Antagonist for Axon Tract Formation
Sato Y, Iketani M, Kurihara Y, Yamaguchi M, Yamashita N, Nakamura F, Arie Y, Kawasaki T, Hirata T, Abe T, Kiyonari H, Strittmatter SM, Goshima Y, Takei K. Cartilage Acidic Protein–1B (LOTUS), an Endogenous Nogo Receptor Antagonist for Axon Tract Formation. Science 2011, 333: 769-773. PMID: 21817055, PMCID: PMC3244695, DOI: 10.1126/science.1204144.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBinding SitesCalcium-Binding ProteinsCell LineCells, CulturedGPI-Linked ProteinsGrowth ConesHumansImmunohistochemistryLigandsMiceMice, Inbred ICRMyelin ProteinsNogo ProteinsNogo Receptor 1Olfactory PathwaysProsencephalonProtein BindingReceptors, Cell SurfaceSignal TransductionConceptsTract formationNogo receptor 1Axon growth inhibitorsProtein 1BEndogenous antagonismAxon tract formationReceptor antagonistGrowth cone collapseAxonal projectionsCircuitry formationNeural circuitry formationMouse brainReceptor 1LOT formationNeural regenerationNgR1Key moleculesCone collapseMiceFluorophore-assisted light inactivationGrowth inhibitorAntagonistBrainMyelinNogo
2010
Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin
Hu F, Padukkavidana T, Vægter CB, Brady OA, Zheng Y, Mackenzie IR, Feldman HH, Nykjaer A, Strittmatter SM. Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin. Neuron 2010, 68: 654-667. PMID: 21092856, PMCID: PMC2990962, DOI: 10.1016/j.neuron.2010.09.034.Peer-Reviewed Original ResearchConceptsFrontotemporal lobar degenerationSerum PGRN levelsFTLD-TDP casesFTLD-TDPMicroglial cellsPGRN levelsCortical neuronsGRN haploinsufficiencyProgranulin mutationsTDP-43Causative rolePGRNUbiquitin aggregatesNeuronsSortilinMiceCell surfaceDetermine levelsPathophysiologyInjuryProgranulinCNSCentral roleDegenerationBrain
2009
Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature 2009, 457: 1128-1132. PMID: 19242475, PMCID: PMC2748841, DOI: 10.1038/nature07761.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAmyloidosisAnimalsChlorocebus aethiopsCOS CellsHippocampusHumansLong-Term PotentiationMiceMice, Inbred C57BLNeuronal PlasticityNeuronsPeptide FragmentsPrionsProtein BindingProtein MultimerizationReceptors, Cell SurfaceSynapsesConceptsCellular prion protein PrPCPrion protein PrPCSoluble amyloid-β peptide (Aβ) oligomersAlzheimer's diseaseCellular prion proteinDisease pathologyPlasma membrane glycoproteinsCell surface receptorsHigh affinity cell surface receptorsAlzheimer's disease pathologySoluble Aβ oligomersLipid raftsInfectious prion diseasesUnexpected linkMechanistic basisMembrane glycoproteinsPrion proteinAmyloid-β peptide (Aβ) oligomersSynaptic plasticityPrion diseasesTherapeutic potentialDiseaseAβ oligomersCentral roleDeleterious effects
2008
Release of MICAL Autoinhibition by Semaphorin-Plexin Signaling Promotes Interaction with Collapsin Response Mediator Protein
Schmidt EF, Shim SO, Strittmatter SM. Release of MICAL Autoinhibition by Semaphorin-Plexin Signaling Promotes Interaction with Collapsin Response Mediator Protein. Journal Of Neuroscience 2008, 28: 2287-2297. PMID: 18305261, PMCID: PMC2846290, DOI: 10.1523/jneurosci.5646-07.2008.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell Adhesion MoleculesCell Line, TransformedChick EmbryoCytoskeletal ProteinsFlavin-Adenine DinucleotideGanglia, SpinalGenetic VectorsHIVHumansImmunoprecipitationIntracellular Signaling Peptides and ProteinsLIM Domain ProteinsMembrane GlycoproteinsMicrofilament ProteinsMixed Function OxygenasesMutationNerve Tissue ProteinsNeuritesNeuronsPeptide FragmentsProtein BindingSemaphorin-3ASemaphorinsSignal TransductionTransfectionConceptsCollapsin response mediator proteinsMediator proteinsCytoplasmic proteinsEnzymatic domainsCatalytic domainPlexin functionPlexin receptorsTerminal domainMICALPromotes interactionAxon guidanceNeuronal developmentAxonal guidanceEnzymatic activityProteinAutoinhibitionDomainPlexinsSignalingSemaphorinsActivatorAssociatesInteractionActivityActivation
2006
Characterization of Myelin Ligand Complexes with Neuronal Nogo-66 Receptor Family Members*
Lauré;n J, Hu F, Chin J, Liao J, Airaksinen MS, Strittmatter SM. Characterization of Myelin Ligand Complexes with Neuronal Nogo-66 Receptor Family Members*. Journal Of Biological Chemistry 2006, 282: 5715-5725. PMID: 17189258, PMCID: PMC2852886, DOI: 10.1074/jbc.m609797200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsAxonsCentral Nervous SystemChlorocebus aethiopsCOS CellsGPI-Linked ProteinsHumansLectinsLigandsModels, MolecularMyelin ProteinsMyelin-Associated GlycoproteinNeoplasm ProteinsNerve Tissue ProteinsNogo Receptor 1Protein BindingProtein Structure, TertiaryReceptors, Cell SurfaceRegenerationSubcutaneous Nogo Receptor Removes Brain Amyloid-β and Improves Spatial Memory in Alzheimer's Transgenic Mice
Park JH, Widi GA, Gimbel DA, Harel NY, Lee DH, Strittmatter SM. Subcutaneous Nogo Receptor Removes Brain Amyloid-β and Improves Spatial Memory in Alzheimer's Transgenic Mice. Journal Of Neuroscience 2006, 26: 13279-13286. PMID: 17182778, PMCID: PMC2856604, DOI: 10.1523/jneurosci.4504-06.2006.Peer-Reviewed Original ResearchConceptsAmyloid precursor proteinTransgenic miceAlzheimer's diseaseAbeta clearanceAbeta plaque loadAlzheimer's transgenic miceImproved spatial memoryRadial arm water mazeNogo-66 receptorEffective therapeutic approachPotential therapeutic benefitSpatial memoryAmyloid-beta peptidePlaque loadAbeta levelsBrain amyloidDisease onsetAbeta productionTherapeutic approachesNogo receptorTherapeutic benefitWater mazeInverse correlationAbetaMiceIdentification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells
Miao RQ, Gao Y, Harrison KD, Prendergast J, Acevedo LM, Yu J, Hu F, Strittmatter SM, Sessa WC. Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 10997-11002. PMID: 16835300, PMCID: PMC1544163, DOI: 10.1073/pnas.0602427103.Peer-Reviewed Original ResearchConceptsAmino terminusNogo isoformsHeterologous expression systemDiscovery of agonistsLoop domainNative endothelial cellsEndothelial cellsExpression systemCell spreadingTube formationTerminusNogo-66 receptorIsoformsChemotaxisReceptorsAngiogenesisCellsMorphogenesisVascular remodelingIdentificationPathwayRemodelingNogoVascular functionCardiovascular function
2003
Structure and axon outgrowth inhibitor binding of the Nogo‐66 receptor and related proteins
Barton WA, Liu BP, Tzvetkova D, Jeffrey PD, Fournier AE, Sah D, Cate R, Strittmatter SM, Nikolov DB. Structure and axon outgrowth inhibitor binding of the Nogo‐66 receptor and related proteins. The EMBO Journal 2003, 22: 3291-3302. PMID: 12839991, PMCID: PMC165649, DOI: 10.1093/emboj/cdg325.Peer-Reviewed Original Research
2002
Truncated Soluble Nogo Receptor Binds Nogo-66 and Blocks Inhibition of Axon Growth by Myelin
Fournier AE, Gould GC, Liu BP, Strittmatter SM. Truncated Soluble Nogo Receptor Binds Nogo-66 and Blocks Inhibition of Axon Growth by Myelin. Journal Of Neuroscience 2002, 22: 8876-8883. PMID: 12388594, PMCID: PMC6757674, DOI: 10.1523/jneurosci.22-20-08876.2002.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsCell LineChick EmbryoGPI-Linked ProteinsGrowth ConesHumansKidneyMiceMolecular Sequence DataMutagenesis, Site-DirectedMyelin ProteinsMyelin SheathNeuritesNogo ProteinsNogo Receptor 1Peptide FragmentsProtein BindingProtein Structure, TertiaryReceptors, Cell SurfaceRepetitive Sequences, Amino AcidRetinaSequence DeletionSignal TransductionSolubilityConceptsChick retinal ganglion cellsRetinal ganglion cellsOutgrowth inhibitionMechanism of NogoGanglion cellsNogo receptorOutgrowth inhibitorViral infectionMyelin inhibitionInhibitory signalingNogo-66Axon growthCNS myelinAxon outgrowthMyelinRegenerative growthNogoCOS-7 cellsInhibitionAlkaline phosphataseReceptorsNGR
1999
Plexin-Neuropilin-1 Complexes Form Functional Semaphorin-3A Receptors
Takahashi T, Fournier A, Nakamura F, Wang L, Murakami Y, Kalb R, Fujisawa H, Strittmatter S. Plexin-Neuropilin-1 Complexes Form Functional Semaphorin-3A Receptors. Cell 1999, 99: 59-69. PMID: 10520994, DOI: 10.1016/s0092-8674(00)80062-8.Peer-Reviewed Original Research
1998
Neuropilin-1 Extracellular Domains Mediate Semaphorin D/III-Induced Growth Cone Collapse
Nakamura F, Tanaka M, Takahashi T, Kalb R, Strittmatter S. Neuropilin-1 Extracellular Domains Mediate Semaphorin D/III-Induced Growth Cone Collapse. Neuron 1998, 21: 1093-1100. PMID: 9856464, DOI: 10.1016/s0896-6273(00)80626-1.Peer-Reviewed Original Research