2020
Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy
Tang SJ, Fesharaki-Zadeh A, Takahashi H, Nies SH, Smith LM, Luo A, Chyung A, Chiasseu M, Strittmatter SM. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathologica Communications 2020, 8: 96. PMID: 32611392, PMCID: PMC7329553, DOI: 10.1186/s40478-020-00976-9.Peer-Reviewed Original ResearchConceptsRepetitive closed head injuriesMemory deficitsPhospho-tau accumulationChronic variable stressPersistent memory deficitsP301S transgenic miceClosed head injuryFyn inhibitionPassive avoidance learningFyn kinaseGlial activationPhospho-tauPresynaptic markersSynapse lossTau accumulationHead injurySynapse densityPhosphorylated tauTherapeutic benefitTransgenic miceBehavioral improvementTrauma modelTauopathiesSpatial memoryAvoidance learning
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 efficacyRescue of Transgenic Alzheimer’s Pathophysiology by Polymeric Cellular Prion Protein Antagonists
Gunther EC, Smith LM, Kostylev MA, Cox TO, Kaufman AC, Lee S, Folta-Stogniew E, Maynard GD, Um JW, Stagi M, Heiss JK, Stoner A, Noble GP, Takahashi H, Haas LT, Schneekloth JS, Merkel J, Teran C, Naderi Z, Supattapone S, Strittmatter SM. Rescue of Transgenic Alzheimer’s Pathophysiology by Polymeric Cellular Prion Protein Antagonists. Cell Reports 2019, 26: 145-158.e8. PMID: 30605671, PMCID: PMC6358723, DOI: 10.1016/j.celrep.2018.12.021.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseOligomeric β-amyloid peptideAPPswe/PS1ΔE9 transgenic miceEffective brain concentrationsPotential therapeutic approachΒ-amyloid peptideBrain concentrationsSynapse lossTherapeutic approachesAlzheimer's pathophysiologyTransgenic miceScN2a cellsMemory deficitsCellular prion proteinPathophysiologyTransmissible spongiformAβOsProtein antagonistLow nanomolar affinityDiseasePrPPrion proteinNanomolar affinitySupAntagonist
2015
Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1−/− Mice
Fink KL, Strittmatter SM, Cafferty WB. Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1−/− Mice. Journal Of Neuroscience 2015, 35: 15403-15418. PMID: 26586827, PMCID: PMC4649010, DOI: 10.1523/jneurosci.3165-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAmidinesAnalysis of VarianceAnimalsAxonsBiotinCrystallinsDextransDisease Models, AnimalFunctional LateralityGene Expression RegulationGlial Fibrillary Acidic ProteinGPI-Linked ProteinsLuminescent ProteinsMiceMice, Inbred C57BLMice, TransgenicMu-CrystallinsMyelin ProteinsNerve RegenerationNogo Receptor 1Pyramidal TractsReceptors, Cell SurfaceRecovery of FunctionSpinal Cord InjuriesConceptsCorticospinal tractCST axonsTransgenic miceMotor tractsDextran amineFunctional deficitsSpinal cordAxon regenerationSpinal Cord Injury StudySpontaneous axon regenerationSpinal cord traumaNogo receptor 1Permanent functional deficitsPersistent functional deficitsBilateral pyramidotomyDorsal hemisectionMidthoracic cordCord traumaMotor pathwaysAdult CNSCST regenerationInjury studiesLesion siteRegenerating fibersNeural repairFyn inhibition rescues established memory and synapse loss in Alzheimer mice
Kaufman AC, Salazar SV, Haas LT, Yang J, Kostylev MA, Jeng AT, Robinson SA, Gunther EC, van Dyck CH, Nygaard HB, Strittmatter SM. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Annals Of Neurology 2015, 77: 953-971. PMID: 25707991, PMCID: PMC4447598, DOI: 10.1002/ana.24394.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseTransgenic miceGlu receptorsAPP/PS1 transgenic miceAPP/PS1 miceMemory deficitsEffective disease-modifying agentsAD mouse modelPS1 transgenic miceAD transgenic miceDisease-modifying agentsTau transgenic miceWeeks of treatmentPrecursor protein metabolismSpatial memory deficitsNovel object recognitionMorris water mazeBrain slice assaysAZD0530 treatmentMicroglial activationPS1 miceVehicle treatmentSynapse lossAlzheimer's miceAD pathology
2010
Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse
Chung E, Ji Y, Sun Y, Kascsak RJ, Kascsak RB, Mehta PD, Strittmatter SM, Wisniewski T. Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse. BMC Neuroscience 2010, 11: 130. PMID: 20946660, PMCID: PMC2964735, DOI: 10.1186/1471-2202-11-130.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsAntibodies, MonoclonalBlotting, WesternCerebral CortexCognition DisordersEnzyme-Linked Immunosorbent AssayHippocampusHumansImage Processing, Computer-AssistedImmunohistochemistryMemory, Short-TermMiceMice, TransgenicPrPC ProteinsPsychomotor PerformanceSynapsesSynaptophysinConceptsAPP/PS1 Tg miceAPP/PS1 transgenic miceAPP/PS1 TgPS1 transgenic miceDisease model miceTransgenic miceCognitive deficitsTg miceAβ oligomersBehavioral testingVehicle solutionAlzheimer's disease model miceDentate gyrus molecular layerAPP/PS1 groupWild-type control groupConformational neurodegenerative disordersMonoclonal antibody infusionAD transgenic miceAmyloid plaque burdenAβ oligomer levelsDays/weekNovel therapeutic approachesMurine hippocampal slicesShort-term treatmentAnti-PrP antibodiesLaurén et al. reply
Laurén J, Gimbel D, Nygaard H, Gilbert J, Strittmatter S. Laurén et al. reply. Nature 2010, 466: e4-e5. DOI: 10.1038/nature09218.Peer-Reviewed Original ResearchDisease model miceTransgenic Alzheimer's disease model miceAlzheimer's disease model miceDisease miceModel miceDisease progressionTransgenic Alzheimer's disease miceSpatial learningAlzheimer's disease miceAlzheimer's disease progressionSynapse lossAxonal degenerationEarly deathTransgenic miceCellular prion proteinMicePrion proteinPrPCDeficitsExpression cloningDirect assessmentDegenerationMemory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein
Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Laurén J, Gimbel ZA, Strittmatter SM. Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein. Journal Of Neuroscience 2010, 30: 6367-6374. PMID: 20445063, PMCID: PMC3323924, DOI: 10.1523/jneurosci.0395-10.2010.Peer-Reviewed Original ResearchConceptsTransgenic miceAlzheimer's diseaseCellular prion proteinSpatial learningAD transgenic miceTransgenic AD modelTransgenic Alzheimer's micePrnp-/- miceAD-related phenotypesAmyloid-beta peptideAbeta accumulationAbeta plaquesAbeta levelsAD micePrion proteinAlzheimer's miceAxonal degenerationAPP expressionSynaptic markersHippocampal slicesDetectable impairmentEarly deathAD modelBehavioral impairmentsMemory impairment
2007
Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice.
Park JH, Strittmatter SM. Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice. Current Alzheimer Research 2007, 4: 568-70. PMID: 18220524, PMCID: PMC2846284, DOI: 10.2174/156720507783018235.Peer-Reviewed Original ResearchConceptsTransgenic miceAlzheimer's diseasePlaque depositionAdult central nervous systemAlzheimer's transgenic miceNogo-66 receptorAmyloid β plaquesCentral nervous systemAxonal sproutingAβ accumulationΒ plaquesDystrophic neuritesPathologic changesNogo receptorNervous systemBrain APPDiseasePotential mechanistic basisMiceExpression increasesNGR modificationReceptorsNeurite responseNGRMechanistic basisFunctional Axonal Regeneration through Astrocytic Scar Genetically Modified to Digest Chondroitin Sulfate Proteoglycans
Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM. Functional Axonal Regeneration through Astrocytic Scar Genetically Modified to Digest Chondroitin Sulfate Proteoglycans. Journal Of Neuroscience 2007, 27: 2176-2185. PMID: 17329414, PMCID: PMC2848955, DOI: 10.1523/jneurosci.5176-06.2007.Peer-Reviewed Original ResearchConceptsChondroitin sulfate proteoglycanRole of CSPGsTransgenic miceSensory axon regenerationMotor function recoveryFunctional axonal regenerationCombination-based therapyEnzyme chondroitinase ABCSulfate proteoglycanDorsal hemisectionAxotomized neuronsDorsal rhizotomyCorticospinal axonsCNS injuryFunction recoveryMyelin inhibitorsAxonal regenerationAstrocytic scarLocal efficacyTraumatic injuryAxon regenerationLesion siteInhibitory moleculesFunctional regenerationChondroitinase ABC
2006
Subcutaneous 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
2003
Nogo-C is sufficient to delay nerve regeneration
Kim J, Bonilla IE, Qiu D, Strittmatter SM. Nogo-C is sufficient to delay nerve regeneration. Molecular And Cellular Neuroscience 2003, 23: 451-459. PMID: 12837628, DOI: 10.1016/s1044-7431(03)00076-9.Peer-Reviewed Original ResearchConceptsAxonal regenerationTransgenic miceSciatic nerve injurySciatic nerve crushAxon growth inhibitorsWild-type miceCentral nervous systemC transgenic miceDecreased recovery ratePeripheral Schwann cellsNerve injuryNerve crushMotor functionPeripheral clearanceSchwann cellsCNS expressionNerve regenerationNervous systemAdult mammalsMiceNogoCellsGrowth inhibitorExpressionInjury