2019
Anti‐PrPC antibody rescues cognition and synapses in transgenic alzheimer mice
Cox TO, Gunther EC, Brody AH, Chiasseu MT, Stoner A, Smith LM, Haas LT, Hammersley J, Rees G, Dosanjh B, Groves M, Gardener M, Dobson C, Vaughan T, Chessell I, Billinton A, Strittmatter SM. Anti‐PrPC antibody rescues cognition and synapses in transgenic alzheimer mice. Annals Of Clinical And Translational Neurology 2019, 6: 554-574. PMID: 30911579, PMCID: PMC6414488, DOI: 10.1002/acn3.730.Peer-Reviewed Original ResearchConceptsAPP/PS1 transgenic micePS1 transgenic miceBrain antibodiesTransgenic miceDisease pathophysiologyDisease pathologyTransgenic Alzheimer's miceAlzheimer's disease pathologyAlzheimer's disease pathophysiologyHuman monoclonal antibodyPreclinical therapeutic efficacyHigh-affinity receptorAmyloid-beta oligomersLast doseTransgenic brainsPlaque pathologyAlzheimer's micePreclinical dataSynaptic damageAnti-PrPc antibodiesSynaptic densityIntraperitoneal dosingBrain biochemistryCentral synapsesTherapeutic efficacyPlexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma
Sekine Y, Algarate PT, Cafferty WBJ, Strittmatter SM. Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma. Journal Of Neuroscience 2019, 39: 3204-3216. PMID: 30804090, PMCID: PMC6788813, DOI: 10.1523/jneurosci.2996-18.2019.Peer-Reviewed Original ResearchConceptsCNS traumaNeural repairMouse cervical spinal cordSpinal cord traumaCervical spinal cordNon-neuronal cellsInteraction of NogoAxon growth inhibitionAxonal guidance mechanismsNeurological recoveryAxonal sproutingCNS pathwaysCord traumaFunctional recoveryAxon sproutingSpinal cordNgR1 functionUnilateral pyramidotomyAxon regenerationAdult traumaNgR1TraumaAxon growthNogoCytoplasmic mediatorsSystematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance
Smith LM, Kostylev MA, Lee S, Strittmatter SM. Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance. Journal Of Biological Chemistry 2019, 294: 6042-6053. PMID: 30787106, PMCID: PMC6463724, DOI: 10.1074/jbc.ra118.006252.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD brainLeukocyte immunoglobulin-like receptorsNogo receptor 1Human AD brainsImmunoglobulin-like receptorsB member 2Brains of individualsReceptor candidatesSoluble AβOsDisease relevanceCell surface expressionHippocampal neuronsMouse modelSynthetic AβAβO bindingMemory impairmentReceptor 1Cellular prion proteinNeuronal synapsesNgR1Molecular pathologyAβAβ speciesMember 2
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 domainsSpeciesDomainProteinAβOsThe nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury
Sekine Y, Siegel CS, Sekine-Konno T, Cafferty WBJ, Strittmatter SM. The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury. Science Signaling 2018, 11 PMID: 29615517, PMCID: PMC6179440, DOI: 10.1126/scisignal.aao4180.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCord injuryAxonal regenerationMid-thoracic spinal cordTraumatic spinal cord injuryPartial neurological recoveryTraumatic CNS injuryDorsal hemisectionNeurological recoveryPeptide nociceptinCNS injuryAxon sproutingORL1 agonistSelective blockadeSpinal cordLocomotor functionNociceptin receptorAxon regenerationNeural repairPrimary neuronsNgR1 proteinAxonal growthNull miceMRNA expressionORL1
2015
Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway
Nakatsu F, Messa M, Nández R, Czapla H, Zou Y, Strittmatter SM, De Camilli P. Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway. Journal Of Cell Biology 2015, 209: 85-95. PMID: 25869668, PMCID: PMC4395491, DOI: 10.1083/jcb.201409064.Peer-Reviewed Original ResearchConceptsEndocytic membranesPosition of inositolRecruitment of inositolSAC domainEndocytic pathwayPlasma membraneINPP5FSequential dephosphorylationOCRLDephosphorylationEndocytosisSynaptojaninRab5EndosomesYeastInositolMembranePhosphataseMacropinosomesClathrinCoimmunoprecipitationPtdInsPhosphoinositideVesiclesPathway
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
β-amyloid oligomers and cellular prion protein in Alzheimer’s disease
Gunther EC, Strittmatter SM. β-amyloid oligomers and cellular prion protein in Alzheimer’s disease. Journal Of Molecular Medicine 2009, 88: 331-338. PMID: 19960174, PMCID: PMC2846635, DOI: 10.1007/s00109-009-0568-7.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseAβ oligomersDisease pathophysiologyCellular prion proteinProgression of ADAlzheimer's disease pathophysiologyΒ-amyloid oligomersΒ-amyloid peptidePrion proteinBrain slicesAlzheimer's diseaseSynaptic functionFunctional receptorsNeurodegenerative diseasesDiseasePotential mediatorsAβ assembliesReceptorsAβ monomersPrPCPathophysiologyNeurotoxicityPlaquesProgressionReticulon-4A (Nogo-A) Redistributes Protein Disulfide Isomerase to Protect Mice from SOD1-Dependent Amyotrophic Lateral Sclerosis
Yang YS, Harel NY, Strittmatter SM. Reticulon-4A (Nogo-A) Redistributes Protein Disulfide Isomerase to Protect Mice from SOD1-Dependent Amyotrophic Lateral Sclerosis. Journal Of Neuroscience 2009, 29: 13850-13859. PMID: 19889996, PMCID: PMC2797811, DOI: 10.1523/jneurosci.2312-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmyotrophic Lateral SclerosisAnimalsChlorocebus aethiopsCOS CellsGlycineMaleMiceMice, CongenicMice, Inbred C57BLMice, KnockoutMice, TransgenicMolecular ChaperonesMyelin ProteinsNeuroprotective AgentsNogo ProteinsProtein Disulfide-IsomerasesSuperoxide DismutaseSuperoxide Dismutase-1Tissue DistributionConceptsAmyotrophic lateral sclerosisLateral sclerosisFatal motor neuron diseaseSubset of patientsALS disease progressionMotor neuron diseaseTransgenic mouse modelPotential therapeutic approachEndoplasmic reticulum stressHomogeneous expression patternNeuron diseaseALS pathophysiologyDisease onsetDisease progressionTherapeutic approachesMouse modelChaperone protein disulfide isomeraseReticulum stressNovel intracellular roleReticulon proteinsMiceSclerosisPatientsUnfolded protein responseNogoALGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology
Owuor K, Harel NY, Englot DJ, Hisama F, Blumenfeld H, Strittmatter SM. LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. Molecular And Cellular Neuroscience 2009, 42: 448-457. PMID: 19796686, PMCID: PMC2783222, DOI: 10.1016/j.mcn.2009.09.008.Peer-Reviewed Original ResearchConceptsNeuronal morphologyAutosomal dominant partial epilepsyCA1 pyramidal neuronsSeizure thresholdSpontaneous seizuresPartial epilepsyPyramidal neuronsDendritic arborizationLGI1PSD-95LGI1 geneEpilepsy genesADAM23ADPEAFADAM22EpilepsyNeurite outgrowthIon channelsBrain genesUnbiased screenAuditory featuresOutgrowthSeizuresArborizationRelated proteinsCellular 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
Genetic Variants of Nogo-66 Receptor with Possible Association to Schizophrenia Block Myelin Inhibition of Axon Growth
Budel S, Padukkavidana T, Liu BP, Feng Z, Hu F, Johnson S, Lauren J, Park JH, McGee AW, Liao J, Stillman A, Kim JE, Yang BZ, Sodi S, Gelernter J, Zhao H, Hisama F, Arnsten AF, Strittmatter SM. Genetic Variants of Nogo-66 Receptor with Possible Association to Schizophrenia Block Myelin Inhibition of Axon Growth. Journal Of Neuroscience 2008, 28: 13161-13172. PMID: 19052207, PMCID: PMC2892845, DOI: 10.1523/jneurosci.3828-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChick EmbryoChlorocebus aethiopsChromosome MappingCodonCOS CellsFemaleGenetic Predisposition to DiseaseGPI-Linked ProteinsGrowth ConesGrowth InhibitorsHumansMaleMiceMice, KnockoutMutationMyelin ProteinsNerve Fibers, MyelinatedNeurogenesisNeuronal PlasticityNogo Receptor 1Organ Culture TechniquesRatsReceptors, Cell SurfaceSchizophreniaConceptsMyelin inhibitionNogo-66 receptorCase-control analysisMyelin-specific genesAxonal sproutingMyelin signalGenetic predispositionAxon inhibitionNeuronal culturesPossible associationReceptor 1Disease riskAxon growthSchizophreniaAxonal proteinsPotential endophenotypeMemory functionGenetic variantsDysfunctional proteinsInhibitionSchizophrenia susceptibilityDominant negativeProtein exhibitCandidate genesChromosome 22q11The N-Terminal Domain of Nogo-A Inhibits Cell Adhesion and Axonal Outgrowth by an Integrin-Specific Mechanism
Hu F, Strittmatter SM. The N-Terminal Domain of Nogo-A Inhibits Cell Adhesion and Axonal Outgrowth by an Integrin-Specific Mechanism. Journal Of Neuroscience 2008, 28: 1262-1269. PMID: 18234903, PMCID: PMC2856844, DOI: 10.1523/jneurosci.1068-07.2008.Peer-Reviewed Original ResearchConceptsCell adhesionFocal adhesion kinase activationN-terminal domainAxonal outgrowthInhibits cell adhesionAxonal growth conesCNS axon regenerationKinase activationCertain integrinsIntegrin activatorIntegrin beta1Widespread expressionExtracellular matrixSecond domainAlpha5 integrinUnknown mechanismIntegrinsGrowth conesNogo-A proteinCell linesAlpha6 integrinNogo-66 receptorAxonal growthAdult brainOutgrowth
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 correlationAbetaMice
2004
Neogenin mediates the action of repulsive guidance molecule
Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller BK, Strittmatter SM. Neogenin mediates the action of repulsive guidance molecule. Nature Cell Biology 2004, 6: 756-762. PMID: 15258590, DOI: 10.1038/ncb1156.Peer-Reviewed Original ResearchConceptsRepulsive guidance moleculeRetinal ganglion cell axonsGuidance moleculesGanglion cell axonsDorsal root ganglion axonsTemporal retinal axonsVisual map formationReceptor mechanismsCell axonsNeogenin expressionRetinal axonsGanglion axonsAxonal responsivenessOptic tectumChick retinaNeogeninSub-nanomolar affinityAxonsAxonal guidanceNeogenin functionsResponsive stateNeural tubeMap formationExpressionRetina
2003
Structural bases for CRMP function in plexin‐dependent semaphorin3A signaling
Deo RC, Schmidt EF, Elhabazi A, Togashi H, Burley SK, Strittmatter SM. Structural bases for CRMP function in plexin‐dependent semaphorin3A signaling. The EMBO Journal 2003, 23: 9-22. PMID: 14685275, PMCID: PMC1271659, DOI: 10.1038/sj.emboj.7600021.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SequenceAmino Acid SubstitutionAnimalsCell Adhesion MoleculesCell LineChick EmbryoChlorocebus aethiopsCOS CellsCrystallography, X-RayGanglia, SpinalHumansHydrogen BondingImmunophilinsMiceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNerve Tissue ProteinsPhosphoproteinsProtein Structure, SecondaryProtein Structure, TertiaryReceptors, Cell SurfaceRecombinant Fusion ProteinsSemaphorin-3ASequence Homology, Amino AcidSignal TransductionStructure-Activity RelationshipConceptsCollapsin response mediator proteinsStructure-based mutagenesisCOS-7 cellsSurface-exposed residuesTetrameric assemblyPhysical complexAxonal specificationMediator proteinsStructural basisFunctional domainsAlanine substitutionsActive proteinCytosolic phosphoproteinNeuronal differentiationAxonal repulsionAxonal guidanceReceptor componentsProteinStructural viewX-ray crystal structureCRMP1Sema3ACell contractionCellsNP1
2002
Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor
Liu BP, Fournier A, GrandPré T, Strittmatter SM. Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor. Science 2002, 297: 1190-1193. PMID: 12089450, DOI: 10.1126/science.1073031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBinding SitesChick EmbryoCloning, MolecularCOS CellsGanglia, SpinalGene LibraryGPI-Linked ProteinsLigandsMiceMyelin ProteinsMyelin-Associated GlycoproteinNerve RegenerationNeuritesNeuronsNogo ProteinsNogo Receptor 1Peptide FragmentsPhosphatidylinositol Diacylglycerol-LyaseProtein Structure, TertiaryReceptors, Cell SurfaceRecombinant Fusion ProteinsSialic AcidsTransfectionType C PhospholipasesSmall Proline-Rich Repeat Protein 1A Is Expressed by Axotomized Neurons and Promotes Axonal Outgrowth
Bonilla IE, Tanabe K, Strittmatter SM. Small Proline-Rich Repeat Protein 1A Is Expressed by Axotomized Neurons and Promotes Axonal Outgrowth. Journal Of Neuroscience 2002, 22: 1303-1315. PMID: 11850458, PMCID: PMC6757578, DOI: 10.1523/jneurosci.22-04-01303.2002.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAxonsAxotomyCell DifferentiationCell Surface ExtensionsCornified Envelope Proline-Rich ProteinsCOS CellsGanglia, SpinalMaleMembrane ProteinsMiceMice, Inbred C57BLNerve CrushNerve RegenerationNeuronsOligonucleotide Array Sequence AnalysisProtein BiosynthesisProteinsRNA, MessengerS100 ProteinsSciatic NerveSciatic NeuropathySpinal Cord InjuriesTransfectionConceptsSmall proline-rich repeat protein 1AProtein 1AAxonal outgrowthMembrane rufflesP21/WAFDifferentiation genesCDNA microarrayNerve regenerationF-actinEpithelial differentiation genesPeripheral axonal damageSciatic nerve regenerationSuccessful nerve regenerationAbility of neuronsSPRR1AGenesUninjured neuronsAxotomized neuronsRange of substratesAxonal damageSensory neuronsOutgrowthNeuronsRufflesAxons
2001
PlexinA1 Autoinhibition by the Plexin Sema Domain
Takahashi T, Strittmatter S. PlexinA1 Autoinhibition by the Plexin Sema Domain. Neuron 2001, 29: 429-439. PMID: 11239433, DOI: 10.1016/s0896-6273(01)00216-1.Peer-Reviewed Original Research