2023
Amino-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 ResearchConceptsAxon regenerationCentral nervous system injuryPersistent neurological deficitsCerebral cortical neuronsNervous system injuryNeurological deficitsSystem injuryCNS injuryCortical neuronsAmino-terminal fragmentInjuryExtracellular actionPhysiological productionNogoInhibitory proteinMiceNeuronsInhibitory domainOverexpression increasesVaried resultsProteolytic fragmentsAxotomyExpressionNogoAGene targeting
2022
Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2
Rodriguez CM, Bechek SC, Jones GL, Nakayama L, Akiyama T, Kim G, Solow-Cordero DE, Strittmatter SM, Gitler AD. Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2. Cell Reports 2022, 41: 111505. PMID: 36288715, PMCID: PMC9664481, DOI: 10.1016/j.celrep.2022.111505.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisSpinocerebellar ataxia type 2Nogo receptorAtaxin-2 levelsNovel therapeutic targetNeurodegenerative disease amyotrophic lateral sclerosisGene-based therapeutic strategiesDisease amyotrophic lateral sclerosisNerve injuryAtaxin-2Axonal regenerationAxonal regrowthLateral sclerosisTherapeutic strategiesHuman neuronsKnockout miceTherapeutic targetPotential treatmentType 2Protein levelsPotent modifierProtein ataxin-2Additional strategiesMiceRNA screenIFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses
Clement M, Forbester J, Marsden M, Sabberwal P, Sommerville M, Wellington D, Dimonte S, Clare S, Harcourt K, Yin Z, Nobre L, Antrobus R, Jin B, Chen M, Makvandi-Nejad S, Lindborg J, Strittmatter S, Weekes M, Stanton R, Dong T, Humphreys I. IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses. Nature Communications 2022, 13: 5294. PMID: 36075894, PMCID: PMC9454482, DOI: 10.1038/s41467-022-32587-4.Peer-Reviewed Original ResearchConceptsInterferon-induced transmembrane protein 3IL-6 productionViral pathogenesisCytokine productionPro-inflammatory cytokine productionInflammatory cytokine productionInflammatory cytokine responseSARS-CoV-2Transmembrane protein 3Dendritic cellsCytokine responsesImmunoregulatory pathwaysImmunoregulatory functionsTLR2 responsesTLR responsesMouse modelMyeloid cellsViral stimulationProtein 3PathogenesisRestriction factorsNogoCellular localizationResponseCells
2021
NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates
Boghdadi AG, Spurrier J, Teo L, Li M, Skarica M, Cao B, Kwan WC, Merson TD, Nilsson SK, Sestan N, Strittmatter SM, Bourne JA. NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates. Nature Communications 2021, 12: 6906. PMID: 34824275, PMCID: PMC8617297, DOI: 10.1038/s41467-021-27245-0.Peer-Reviewed Original ResearchConceptsBrain injuryPeripheral macrophage infiltrationIschemic brain injuryAnti-inflammatory responseMajority of astrocytesNeurite outgrowth inhibitory proteinIschemic strokePeripheral macrophagesReactive astrocytesMacrophage infiltrationStroke recoveryAstrocyte clustersMarmoset monkeysVisual cortexAstrocytesNogoASingle-nucleus transcriptomicsInhibitory proteinInjuryStrokeHuman brainInfiltrationCritical rolePrecise functionOligodendrocytesB-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
Bakhuraysah MM, Theotokis P, Lee JY, Alrehaili AA, Aui PM, Figgett WA, Azari MF, Abou-Afech JP, Mackay F, Siatskas C, Alderuccio F, Strittmatter SM, Grigoriadis N, Petratos S. B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF. Scientific Reports 2021, 11: 2890. PMID: 33536561, PMCID: PMC7858582, DOI: 10.1038/s41598-021-82346-6.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisEAE-induced miceB cellsB-cell activating factorMeningeal B cellsLumbosacral spinal cordSecretion of immunoglobulinsG0/G1 phaseImmune cell signalingNeurological progressionAutoimmune encephalomyelitisInflammatory infiltrateAxonal dystrophyCentral nervous system myelinSpinal cordRecombinant BAFFActivating factorNgR1Score 1BAFFBAFF stimulationInfiltratesNgR3System myelinG1 phase
2019
A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration
Sekine Y, Lindborg JA, Strittmatter SM. A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration. Journal Of Biological Chemistry 2019, 295: 2175-2183. PMID: 31748413, PMCID: PMC7039549, DOI: 10.1074/jbc.ra119.009896.Peer-Reviewed Original ResearchConceptsMembrane-associated proteinsRecombinant protein expressionMatrix-associated proteinOligodendrocyte plasma membraneProteolytic C-terminal fragmentsRegeneration assaysC-terminal fragmentPlasma membraneNeurite outgrowth inhibitor NogoAxonal regenerationExosomal releaseDiffusible inhibitorC-terminalSiRNA knockdownCleavage siteCultured cellsLong fragmentPrimary cortical neuron culturesCentral nervous system traumaExosomesEnzyme inhibitor treatmentExosomal fractionSpinal cord crush injuryCerebral cortex neuronsProteinPlexina2 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 mediators
2016
Axonal branching in lateral olfactory tract is promoted by Nogo signaling
Iketani M, Yokoyama T, Kurihara Y, Strittmatter SM, Goshima Y, Kawahara N, Takei K. Axonal branching in lateral olfactory tract is promoted by Nogo signaling. Scientific Reports 2016, 6: 39586. PMID: 28000762, PMCID: PMC5175167, DOI: 10.1038/srep39586.Peer-Reviewed Original ResearchConceptsLateral olfactory tractCultured OB neuronsOB neuronsCollateral branchesAxonal branchingOlfactory bulbOlfactory tractAxonal bundlesMajor projection neuronsReceptor 1 antagonistKnockdown of NogoCollateral formationProjection neuronsPrimary axonsNogo signalingMitral cellsMiceNeuronsExpression levelsAbnormal increaseTractNogoAntagonistAxons
2015
Plasticity 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
Nogo 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
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 inhibitorAntagonistBrainMyelinNogoMyelin 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 roleA 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
MAG and OMgp Synergize with Nogo-A to Restrict Axonal Growth and Neurological Recovery after Spinal Cord Trauma
Cafferty WB, Duffy P, Huebner E, Strittmatter SM. MAG and OMgp Synergize with Nogo-A to Restrict Axonal Growth and Neurological Recovery after Spinal Cord Trauma. Journal Of Neuroscience 2010, 30: 6825-6837. PMID: 20484625, PMCID: PMC2883258, DOI: 10.1523/jneurosci.6239-09.2010.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBiotinCells, CulturedDextransDisease Models, AnimalFemaleFunctional LateralityGanglia, SpinalGPI-Linked ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutMutationMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNerve Tissue ProteinsNeuronsNogo ProteinsPyramidal TractsReceptors, Cell SurfaceReceptors, SerotoninRecovery of FunctionSpinal Cord InjuriesConceptsAxonal growthSpinal Cord Injury StudyMutant miceGreater axonal growthGreater behavioral recoverySpinal cord traumaWild-type miceAxonal growth inhibitionHeterozygous mutant miceDeficient myelinNeurological recoveryCNS damageTriple-mutant miceBehavioral recoveryCord traumaFunctional recoveryNeurological functionMyelin inhibitorsAxonal regrowthReceptor mechanismsInjury studiesMyelin inhibitionDecoy receptorOptimal chanceMice
2009
Rho-Associated Kinase II (ROCKII) Limits Axonal Growth after Trauma within the Adult Mouse Spinal Cord
Duffy P, Schmandke A, Schmandke A, Sigworth J, Narumiya S, Cafferty WB, Strittmatter SM. Rho-Associated Kinase II (ROCKII) Limits Axonal Growth after Trauma within the Adult Mouse Spinal Cord. Journal Of Neuroscience 2009, 29: 15266-15276. PMID: 19955379, PMCID: PMC2855556, DOI: 10.1523/jneurosci.4650-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnalysis of VarianceAnimalsAxonsBehavior, AnimalBrain InjuriesCA1 Region, HippocampalCells, CulturedCholera ToxinEnzyme InhibitorsGanglia, SpinalGene Expression RegulationMedian NeuropathyMiceMice, Inbred C57BLMice, KnockoutMyelin ProteinsNerve RegenerationNeuronsNogo ProteinsPyridinesReceptors, Calcitonin Gene-Related PeptideRhizotomyRho-Associated KinasesSpinal Cord InjuriesTime FactorsVersicansConceptsSpinal cordCNS traumaFunctional recoveryBasso Mouse Scale scoresSpinal Cord Injury StudyAxonal growthDorsal root entry zoneDorsal root ganglion neuronsAdult mouse spinal cordAxonal growth inhibitorsSpinal cord hemisectionRoot entry zoneSpinal cord injuryCaudal spinal cordMouse spinal cordDorsal hemisectionRaphespinal axonsDorsal rhizotomyCrush injuryCord hemisectionCorticospinal axonsChondroitin sulfate proteoglycanCord injuryGanglion neuronsInjury paradigmsReticulon-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 responseNogoAFunctional outcome is impaired following traumatic brain injury in aging Nogo-A/B-deficient mice
Marklund N, Morales D, Clausen F, Hånell A, Kiwanuka O, Pitkänen A, Gimbel DA, Philipson O, Lannfelt L, Hillered L, Strittmatter SM, McIntosh TK. Functional outcome is impaired following traumatic brain injury in aging Nogo-A/B-deficient mice. Neuroscience 2009, 163: 540-551. PMID: 19555742, PMCID: PMC2756649, DOI: 10.1016/j.neuroscience.2009.06.042.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryHemispheric tissue lossNeurological motor functionWT miceBrain injuryMotor functionCortical impact (CCI) TBILittermate controlsAge-matched wild-type littermate controlsMyelin stainingTissue lossMWM taskWild-type littermate controlsCortical lesion volumeAxonal growth inhibitorsRole of NogoMyelin-derived inhibitorAbsence of NogoNeurological motorPoor prognosisFunctional outcomeHemispheric tissuePathophysiological responsesWT littermatesDeficient mice