2023
Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial
Howard E, Strittmatter S. Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial. Current Opinion In Neurology 2023, 36: 516-522. PMID: 37865850, PMCID: PMC10841037, DOI: 10.1097/wco.0000000000001205.Peer-Reviewed Original ResearchConceptsSpinal cord injuryChronic cervical spinal cord injuryCervical spinal cord injuryRecent clinical trialsCentral nervous systemClinical trialsAnimal studiesNeural repairChronic spinal cord injuryIncomplete spinal cord injuryTraumatic spinal cord injuryAdult mammalian central nervous systemContusion spinal cord injuryTreatment-naïve patientsSpinal cord traumaMammalian central nervous systemNeural repair therapiesUpper extremity strengthNonhuman primate studiesReceptor 1 pathwayNeurological recoveryNeurological deficitsCord traumaMedical therapyChronic stageAmino-terminal proteolytic fragment of the axon growth inhibitor Nogo-A (Rtn4A) is upregulated by injury and promotes axon regeneration
Sekine Y, Wang X, Kikkawa K, Honda S, Strittmatter S. Amino-terminal proteolytic fragment of the axon growth inhibitor Nogo-A (Rtn4A) is upregulated by injury and promotes axon regeneration. Journal Of Biological Chemistry 2023, 299: 105232. PMID: 37690690, PMCID: PMC10622843, DOI: 10.1016/j.jbc.2023.105232.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsFemaleGrowth InhibitorsMammalsMiceMice, Inbred C57BLMyelin ProteinsNerve RegenerationNogo ProteinsProteolysisConceptsAxon regenerationCentral nervous system injuryPersistent neurological deficitsCerebral cortical neuronsNervous system injuryNeurological deficitsSystem injuryCNS injuryCortical neuronsAmino-terminal fragmentInjuryExtracellular actionPhysiological productionNogoInhibitory proteinMiceNeuronsInhibitory domainOverexpression increasesVaried resultsProteolytic fragmentsAxotomyExpressionNogoAGene targeting
2020
Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury
Wang X, Zhou T, Maynard GD, Terse PS, Cafferty WB, Kocsis JD, Strittmatter SM. Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury. Brain 2020, 143: 1697-1713. PMID: 32375169, PMCID: PMC7850069, DOI: 10.1093/brain/awaa116.Peer-Reviewed Original ResearchConceptsPrimate spinal cord injurySpinal cord injuryCord injuryFemale African green monkeysTreatment-related adverse eventsChronic neurological deficitsNogo receptor 1Left motor cortexRecovery of functionPreclinical rodent modelsSpinal cord injury animalsAfrican green monkeysRaphespinal fibersAdverse eventsCervical cordNeurological deficitsSurgical complicationsCNS traumaTreatment cessationCorticospinal axonsLumbar catheterInjury animalsNeural recoverySpontaneous feedingLateral hemisection
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 repairPlasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury
Siegel CS, Fink KL, Strittmatter SM, Cafferty WB. Plasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury. Journal Of Neuroscience 2015, 35: 1443-1457. PMID: 25632122, PMCID: PMC4308593, DOI: 10.1523/jneurosci.3713-14.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDesigner DrugsFunctional LateralityGene Expression RegulationGlial Fibrillary Acidic ProteinLocomotionMaleMiceMice, Inbred C57BLMice, TransgenicMuscle StrengthMyelin ProteinsNeuronal PlasticityNogo ProteinsPsychomotor DisordersPyramidal TractsRaphe NucleiRecovery of FunctionSpinal Cord InjuriesStereotyped BehaviorTime FactorsConceptsSpinal cord injurySpontaneous functional recoveryFunctional recoverySpontaneous recoveryIncomplete spinal cord injuryCorticospinal tract lesionsWeeks of lesionCorticospinal tract injuryNogo receptor 1Nucleus raphe magnusTract injuryRubrospinal projectionsTract lesionsCord injuryRaphe magnusCircuit rearrangementsAdult CNSCircuit plasticityLocomotor functionAdult micePharmacogenetic toolsRed nucleusRubral projectionReceptor 1Extensive sprouting
2014
Human NgR-Fc Decoy Protein via Lumbar Intrathecal Bolus Administration Enhances Recovery from Rat Spinal Cord Contusion
Wang X, Yigitkanli K, Kim CY, Sekine-Konno T, Wirak D, Frieden E, Bhargava A, Maynard G, Cafferty WB, Strittmatter SM. Human NgR-Fc Decoy Protein via Lumbar Intrathecal Bolus Administration Enhances Recovery from Rat Spinal Cord Contusion. Journal Of Neurotrauma 2014, 31: 1955-1966. PMID: 24964223, PMCID: PMC4245872, DOI: 10.1089/neu.2014.3355.Peer-Reviewed Original ResearchConceptsSpinal cord injuryTraumatic spinal cord injurySpinal cord contusionNeurological recoveryCord contusionRat spinal cord contusionSpinal contusion injuryLumbar intrathecal spaceLumbar spinal cordContinuous intracerebroventricular infusionRodent SCI modelsPercentage of ratsRaphespinal axonsContusion injuryAdministration regimenSCI modelContinuous infusionCord injuryIntracerebroventricular infusionIntrathecal spaceSpinal cordPreclinical modelsEffective treatmentWalking tasksClinical testingThe Nogo Receptor NgR1 Mediates Infection by Mammalian Reovirus
Konopka-Anstadt JL, Mainou BA, Sutherland DM, Sekine Y, Strittmatter SM, Dermody TS. The Nogo Receptor NgR1 Mediates Infection by Mammalian Reovirus. Cell Host & Microbe 2014, 15: 681-691. PMID: 24922571, PMCID: PMC4100558, DOI: 10.1016/j.chom.2014.05.010.Peer-Reviewed Original ResearchConceptsCentral nervous systemReceptor NgR1Reovirus infectionExpression of NgR1Primary cortical neuronsDistinct cell surface moleculesJunctional adhesion molecule ASoluble NgR1Cell surface moleculesNeurotropic virusesCortical neuronsMammalian reovirusesNonsusceptible cellsNervous systemNgR1Null miceSystemic spreadInfectionIndependent receptorsMultiple receptorsReovirus replicationInitial siteReovirus virionsNeuronsReceptorsNogo limits neural plasticity and recovery from injury
Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Current Opinion In Neurobiology 2014, 27: 53-60. PMID: 24632308, PMCID: PMC4122629, DOI: 10.1016/j.conb.2014.02.011.Peer-Reviewed Original ResearchConceptsNeural repairCentral nervous system injuryOptic nerve injurySpinal cord traumaNervous system injuryExperience-dependent plasticityIschemic strokeNerve injuryCord traumaFunctional recoveryMultiple sclerosisSystem injuryReceptor NgR1Neural plasticityPhysiologic roleAxonal anatomyInjuryAdult mammalsMultiple studiesNogoNgR1Molecular studiesRepairSclerosisAntagonist
2013
Anatomical Plasticity of Adult Brain Is Titrated by Nogo Receptor 1
Akbik FV, Bhagat SM, Patel PR, Cafferty WB, Strittmatter SM. Anatomical Plasticity of Adult Brain Is Titrated by Nogo Receptor 1. Neuron 2013, 77: 859-866. PMID: 23473316, PMCID: PMC3594793, DOI: 10.1016/j.neuron.2012.12.027.Peer-Reviewed Original ResearchConceptsNgr1-/- miceNogo receptor 1Somatosensory cortexReceptor 1Adult cerebral cortexDendritic spine turnoverDendritic spine dynamicsAnatomical plasticityCerebral cortexControl miceSpine turnoverAxonal varicositiesWhisker removalAdult brainDendritic spinesSpine dynamicsNull miceAge 26Synaptic turnoverAnatomical connectivityConditional deletionMiceLower set pointNgR1Cortex
2012
Axonal regeneration induced by blockade of glial inhibitors coupled with activation of intrinsic neuronal growth pathways
Wang X, Hasan O, Arzeno A, Benowitz LI, Cafferty WB, Strittmatter SM. Axonal regeneration induced by blockade of glial inhibitors coupled with activation of intrinsic neuronal growth pathways. Experimental Neurology 2012, 237: 55-69. PMID: 22728374, PMCID: PMC3418451, DOI: 10.1016/j.expneurol.2012.06.009.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsAxonal regenerationPharmacological approachesCrush injuryChondroitin sulfate proteoglycanInjury siteNeural repairOptic nerve crush injuryDorsal root ganglion neuronsNgr1-/- miceNerve crush injurySciatic nerve axotomySpinal cord injury sitePrimary afferent fibersEffective pharmacological approachSpinal cord injuryAdult mammalian neuronsIntrinsic growth potentialGlial inhibitorsTriple therapyNerve axotomyViral gene therapyWT miceAfferent fibersCNS injuryLimiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation
Petratos S, Ozturk E, Azari MF, Kenny R, Lee JY, Magee KA, Harvey AR, McDonald C, Taghian K, Moussa L, Aui P, Siatskas C, Litwak S, Fehlings MG, Strittmatter SM, Bernard CC. Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation. Brain 2012, 135: 1794-1818. PMID: 22544872, PMCID: PMC3589918, DOI: 10.1093/brain/aws100.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceAnimalsAntibodiesAxonsCD3 ComplexCell Line, TumorDemyelinating DiseasesDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleGene Expression RegulationGlycoproteinsGPI-Linked ProteinsGreen Fluorescent ProteinsHumansImmunoprecipitationIntercellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMultiple SclerosisMutationMyelin ProteinsMyelin-Oligodendrocyte GlycoproteinNerve DegenerationNerve Tissue ProteinsNeuroblastomaNeurofilament ProteinsNogo Receptor 1Optic NervePeptide FragmentsPhosphorylationReceptors, Cell SurfaceRetinal Ganglion CellsSeverity of Illness IndexSilver StainingSpinal CordTau ProteinsTime FactorsTransduction, GeneticTubulinConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisAxonal degenerationSpinal cordChronic active multiple sclerosis lesionsOptic nerve axonal degenerationNogo-66 receptor 1CRMP-2Axonal growth inhibitorsCollapsin response mediator protein 2Improved clinical outcomesSpinal cord neuronsRetinal ganglion cellsResponse mediator protein 2Central nervous systemViable therapeutic targetAdeno-associated viral vectorMultiple sclerosis lesionsClinical outcomesOptic nerveCord neuronsOligodendrocyte glycoproteinGanglion cells
2011
Recovery from chronic spinal cord contusion after nogo receptor intervention
Wang X, Duffy P, McGee AW, Hasan O, Gould G, Tu N, Harel NY, Huang Y, Carson RE, Weinzimmer D, Ropchan J, Benowitz LI, Cafferty WB, Strittmatter SM. Recovery from chronic spinal cord contusion after nogo receptor intervention. Annals Of Neurology 2011, 70: 805-821. PMID: 22162062, PMCID: PMC3238798, DOI: 10.1002/ana.22527.Peer-Reviewed Original ResearchConceptsChronic spinal cord injurySpinal cord injuryContusion injuryCord injurySpinal cord contusion injuryCentral nervous system injuryBresnahan locomotor scoresOpen-field BassoSpinal hemisection injuryWeight-bearing statusSpinal cord contusionMonths of treatmentNervous system injuryMyelin-derived inhibitorCaudal spinal cordPositron emission tomographyNgR1 pathwayRaphespinal axonsSpinal contusionCord contusionHemisection injuryFunctional recoveryLocomotor scoresSystem injuryControl ratsCartilage 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 inhibitorAntagonistBrainMyelinNogoMembrane-type Matrix Metalloproteinase-3 Regulates Neuronal Responsiveness to Myelin through Nogo-66 Receptor 1 Cleavage*
Ferraro GB, Morrison CJ, Overall CM, Strittmatter SM, Fournier AE. Membrane-type Matrix Metalloproteinase-3 Regulates Neuronal Responsiveness to Myelin through Nogo-66 Receptor 1 Cleavage*. Journal Of Biological Chemistry 2011, 286: 31418-31424. PMID: 21768085, PMCID: PMC3173120, DOI: 10.1074/jbc.m111.249169.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-3Primary neuronsMetalloproteinase-3Neuronal responsesSH-SY5Y neuroblastoma cellsMetalloproteinase-dependent mannerNeuronal responsivenessAxonal regrowthCortical neuronsNeuronal knockdownNgR1Receptor 1Neuroblastoma cellsNeuronsCell surfaceMT3-MMPMyelinSpecific metalloproteinasesGlycosylphosphatidylinositol-anchored receptorInhibitorsPhysiological consequencesCleavage fragmentsCleavage-resistant formMetalloproteinasesReceptorsMyelin associated inhibitors: A link between injury-induced and experience-dependent plasticity
Akbik F, Cafferty WB, Strittmatter SM. Myelin associated inhibitors: A link between injury-induced and experience-dependent plasticity. Experimental Neurology 2011, 235: 43-52. PMID: 21699896, PMCID: PMC3189418, DOI: 10.1016/j.expneurol.2011.06.006.Peer-Reviewed Original ResearchConceptsExperience-dependent plasticityAnatomical rearrangementsNogo-66 receptor 1Spinal cord injuryNeurologic recoveryFunctional recoveryInciting stimulusCNS injuryCord injuryAxonal regenerationAdult CNSInjury studiesAnimal modelsReceptor 1Common receptorPaired-ImmunoglobulinMyelinInhibitorsInjuryAnatomical growthCNSReceptorsWide spectrumExtracellular matrixGrowth inhibitorDifferential but Competitive Binding of Nogo Protein and Class I Major Histocompatibility Complex (MHCI) to the PIR-B Ectodomain Provides an Inhibition of Cells*
Matsushita H, Endo S, Kobayashi E, Sakamoto Y, Kobayashi K, Kitaguchi K, Kuroki K, Söderhäll A, Maenaka K, Nakamura A, Strittmatter SM, Takai T. Differential but Competitive Binding of Nogo Protein and Class I Major Histocompatibility Complex (MHCI) to the PIR-B Ectodomain Provides an Inhibition of Cells*. Journal Of Biological Chemistry 2011, 286: 25739-25747. PMID: 21636572, PMCID: PMC3138294, DOI: 10.1074/jbc.m110.157859.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta 2-MicroglobulinBinding, CompetitiveFemaleHistocompatibility Antigens Class IHLA AntigensHLA-G AntigensHumansImmunologic FactorsInterleukin-6LipopolysaccharidesMast CellsMiceMice, Inbred C57BLMyelin ProteinsMyelin-Associated GlycoproteinNeurotransmitter AgentsNogo ProteinsProtein Structure, TertiaryRatsReceptors, ImmunologicSubstrate SpecificityConceptsMajor histocompatibility complexRecent unexpected findingsClass I major histocompatibility complexI major histocompatibility complexInterleukin-6 releaseClass I MHC moleculesC-terminal ectodomainNovel inhibitory roleCultured mast cellsI MHC moleculesTerminal domainPeripheral toleranceInhibitory receptorsInhibition of cellMast cellsOutgrowth inhibitorB cellsMyeloid cellsImmune systemMHC moleculesNeurite regenerationNovel mechanismNogo proteinEctodomainInhibitory roleInosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke
Zai L, Ferrari C, Dice C, Subbaiah S, Havton LA, Coppola G, Geschwind D, Irwin N, Huebner E, Strittmatter SM, Benowitz LI. Inosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke. Journal Of Neuroscience 2011, 31: 5977-5988. PMID: 21508223, PMCID: PMC3101108, DOI: 10.1523/jneurosci.4498-10.2011.Peer-Reviewed Original ResearchConceptsIntrinsic growth potentialUnilateral strokeSpinal cordLayer 5 pyramidal neuronsForelimb motor areaSimilar functional improvementEnvironmental enrichmentCause of disabilitySkilled forelimb useEffect of treatmentUndamaged cortexReceptor blockersDenervated sidePreoperative levelsNEP1-40Stroke patientsPyramidal neuronsUndamaged hemisphereSkilled reachingTreatment optionsDenervated areaIntact hemisphereReceptor antagonistClinical trialsFunctional improvementA Multi-domain Fragment of Nogo-A Protein Is a Potent Inhibitor of Cortical Axon Regeneration via Nogo Receptor 1*
Huebner EA, Kim BG, Duffy PJ, Brown RH, Strittmatter SM. A Multi-domain Fragment of Nogo-A Protein Is a Potent Inhibitor of Cortical Axon Regeneration via Nogo Receptor 1*. Journal Of Biological Chemistry 2011, 286: 18026-18036. PMID: 21454605, PMCID: PMC3093876, DOI: 10.1074/jbc.m110.208108.Peer-Reviewed Original ResearchConceptsMature cortical neuronsCortical neuronsNogo-66Axon regenerationReceptor 1Central nervous system injuryDorsal root ganglion neuronsNogo-66 receptor 1Expression of PirBMature cortical culturesNogo receptor 1Nervous system injuryNogo-A proteinImmunoglobulin-like receptorsChick dorsal root ganglion neuronsFunctional recoverySystem injuryGanglion neuronsCortical culturesPredominant receptorNgR1Genetic deletionPirBCell surface receptorsNeurons
2010
Nogo Receptor Deletion and Multimodal Exercise Improve Distinct Aspects of Recovery in Cervical Spinal Cord Injury
Harel NY, Song KH, Tang X, Strittmatter SM. Nogo Receptor Deletion and Multimodal Exercise Improve Distinct Aspects of Recovery in Cervical Spinal Cord Injury. Journal Of Neurotrauma 2010, 27: 2055-2066. PMID: 20809785, PMCID: PMC2978056, DOI: 10.1089/neu.2010.1491.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalExercise TherapyFemaleGene DeletionGenotypeGPI-Linked ProteinsHand StrengthImmunohistochemistryMaleMiceMice, Inbred C57BLMyelin ProteinsNeuronal PlasticityNogo Receptor 1Physical Conditioning, AnimalPostural BalanceReceptors, Cell SurfaceReproducibility of ResultsSerotoninSpinal CordSpinal Cord InjuriesWalkingConceptsSpinal cord injuryCord injuryCervical spinal cord injuryIncomplete spinal cord injuryCervical spinal injurySignificant histological differencesMultimodal exerciseExercise trainingLateral hemisectionReceptor deletionSpinal injuryLesion modelMouse modelAdult miceLesion sizeGene deletionHistological differencesNeural plasticityMild deficitsHistological analysisTraining regimenInjuryPhysical interventionsC3-C4MiceGenetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice
Hånell A, Clausen F, Björk M, Jansson K, Philipson O, Nilsson LN, Hillered L, Weinreb PH, Lee D, McIntosh TK, Gimbel DA, Strittmatter SM, Marklund N. Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice. Journal Of Neurotrauma 2010, 27: 1297-1309. PMID: 20486800, PMCID: PMC2942864, DOI: 10.1089/neu.2009.1255.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryMossy fiber sproutingSoluble NgR1Fiber sproutingBrain injuryCortical impact injury modelEarly post-injury periodNogo-66 receptor 1Hippocampal mossy fiber sproutingBehavioral recovery processSham-injured animalsBrain-injured animalsPost-injury periodSpinal cord injuryOligodendrocyte myelin glycoproteinPharmacological neutralizationBehavioral recoveryFunctional recoveryLoss of tissueCord injuryTimm stainInjury modelMotor functionRodent modelsHistological effects