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
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 functionOligodendrocytes
2018
Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration
Sekine Y, Lin-Moore A, Chenette DM, Wang X, Jiang Z, Cafferty WB, Hammarlund M, Strittmatter SM. Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration. Cell Reports 2018, 23: 415-428. PMID: 29642001, PMCID: PMC5937716, DOI: 10.1016/j.celrep.2018.03.058.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCaenorhabditis elegansCaenorhabditis elegans ProteinsCentral Nervous SystemFemaleGene Regulatory NetworksGenomeMiceMice, Inbred C57BLMice, KnockoutNerve RegenerationOptic NerveRab GTP-Binding ProteinsRecovery of FunctionRetinal Ganglion CellsRNA InterferenceRNA, Small InterferingSpinal Cord InjuriesSuppressor of Cytokine Signaling ProteinsConceptsAxonal regenerationCentral nervous system axonal regenerationRetinal ganglion cell axon regenerationGreater motor functionOptic nerve crushCerebral cortical neuronsSpinal cord traumaNeurological recoveryCord traumaNerve crushCNS injuryAxonal regrowthCortical neuronsMotor functionAxon regenerationReceptor bindingComprehensive functional screenAdult mammalsInjuryMultiple pathwaysExpression profilesIdentifies pathwaysSignificant overlapPathwayFunction screen
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
Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion
Harel NY, Yigitkanli K, Fu Y, Cafferty WB, Strittmatter SM. Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion. Brain Research 2013, 1538: 17-25. PMID: 24055330, PMCID: PMC3873870, DOI: 10.1016/j.brainres.2013.07.012.Peer-Reviewed Original ResearchConceptsBrainstem pathwaysMultimodal exerciseCorticospinal tractTraining groupContext of injuryCST pathwayAnatomical outcomesCST injuryPostural exercisesCorticospinal lesionsCollateral sproutingCST lesionElectrophysiological assessmentSpinal cordPhysical exerciseGait kinematicsLimb performanceSynaptic strengthLesionsSubcortical circuitsFiber densityMiceInjuryFurther studiesExercise
2011
Myelin 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 inhibitor
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 roleDegenerationBrainNogo 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-C4Mice
2009
Axon Regeneration in the Peripheral and Central Nervous Systems
Huebner EA, Strittmatter SM. Axon Regeneration in the Peripheral and Central Nervous Systems. Results And Problems In Cell Differentiation 2009, 48: 305-360. PMID: 19582408, PMCID: PMC2846285, DOI: 10.1007/400_2009_19.Peer-Reviewed Original ResearchConceptsCentral nervous systemPeripheral nervous systemSpinal cord injuryNervous systemAxon regenerationLong-distance axon regenerationMature mammalian central nervous systemMammalian peripheral nervous systemSubstantial functional recoveryMammalian central nervous systemTraumatic brain injuryIntrinsic growth capacityFunctional recoveryCord injuryAxonal disconnectionFunctional deficitsBrain injuryRelated conditionsInjuryRegenerative successExtracellular moleculesGrowth capacityStroke
2008
Axonal growth therapeutics: regeneration or sprouting or plasticity?
Cafferty WB, McGee AW, Strittmatter SM. Axonal growth therapeutics: regeneration or sprouting or plasticity? Trends In Neurosciences 2008, 31: 215-220. PMID: 18395807, PMCID: PMC2678051, DOI: 10.1016/j.tins.2008.02.004.Peer-Reviewed Original ResearchConceptsAxonal growthAstroglial scarHigh clinical significanceFunctional recoveryNeurological injuryInciting eventFunctional deficitsSpinal cordClinical significanceAdult brainLoss of functionCell lossInhibitory factorAxonal connectivityAxonal anatomyAxonal extensionMolecular interventionsMyelinScarCordInjuryBrainFunctional MRI and other non-invasive imaging technologies: Providing visual biomarkers for spinal cord structure and function after injury
Harel NY, Strittmatter SM. Functional MRI and other non-invasive imaging technologies: Providing visual biomarkers for spinal cord structure and function after injury. Experimental Neurology 2008, 211: 324-328. PMID: 18396280, PMCID: PMC2442770, DOI: 10.1016/j.expneurol.2008.02.017.Peer-Reviewed Original ResearchConceptsAxonal growthSpinal cord traumaSpinal cord injurySpinal cord structuresFunctional magnetic resonance imagingMagnetic resonance imagingNon-invasive imaging techniqueCord traumaCord injuryNon-invasive imaging technologyNeurological damageCNS repairFunctional reorganizationTherapeutic interventionsResonance imagingFunctional MRICord structuresInjuryInterventionImaging techniquesVisual biomarkersPotential benefitsCNS structureMolecular basisTraumaPET Imaging of serotonin transporter as a biomarker for axon damage and regeneration in spinal cord injury
Huang Y, Nabulsi N, Weinzimmer D, Fung E, Ropchan J, Labaree D, Wang X, Gould G, Frost J, Carson R, Strittmatter S. PET Imaging of serotonin transporter as a biomarker for axon damage and regeneration in spinal cord injury. NeuroImage 2008, 41: t154. DOI: 10.1016/j.neuroimage.2008.04.122.Peer-Reviewed Original Research
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 SurfaceRegenerationCan regenerating axons recapitulate developmental guidance during recovery from spinal cord injury?
Harel NY, Strittmatter SM. Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury? Nature Reviews Neuroscience 2006, 7: 603-616. PMID: 16858389, PMCID: PMC2288666, DOI: 10.1038/nrn1957.Peer-Reviewed Original ResearchConceptsCNS regenerationNervous systemCentral pattern generatorImmature nervous systemSpinal cord injuryRegeneration-associated genesMammalian CNS regenerationContext of injuryExperience-dependent plasticityFurther plastic changesInflammatory cellsCord injuryVoluntary inputNervous system developmentRegenerating axonsSensory feedbackInhibitory barrierPlastic changesInhibitory moleculesRegenerative responseGuidance moleculesAltered distributionNeuronal branchesInjuryGuidance factorsAxonal Regeneration and Recovery From Chronic Central Nervous System Injury
Strittmatter S. Axonal Regeneration and Recovery From Chronic Central Nervous System Injury. 2006, 1165-1172. DOI: 10.1007/978-1-59259-963-9_122.Peer-Reviewed Original ResearchAxonal regenerationChronic central nervous system injuryCentral nervous system injuryNervous system injuryChronic neurological dysfunctionRecovery of functionTreatment of dysfunctionSystem injuryPersistent dysfunctionNeurological dysfunctionSpinal cordNeurological conditionsAdult brainTrophic factorsNeuronal connectivityDysfunctionNeuronsRecent scientific advancesStem cellsCellsTransplantationCordInjuryBrainRecovery
2005
Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury
Li S, Kim JE, Budel S, Hampton TG, Strittmatter SM. Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury. Molecular And Cellular Neuroscience 2005, 29: 26-39. PMID: 15866044, PMCID: PMC3246391, DOI: 10.1016/j.mcn.2004.12.008.Peer-Reviewed Original ResearchConceptsSpinal cord injuryAxonal sproutingSpinal injuryLumbar spinal cordNogo-66 receptorRecovery of locomotionHemisection injuryCord injurySpinal cordAdult CNSMice exhibitTherapeutic meansAxonal growthReceptor functionNgR ligandsInjuryNogo-66Improved locomotionTransgenic inhibitionMiceSproutingAstrocytesCordCNSOMgpChapter 26 Promoting the Regeneration of Axons within the Central Nervous System
Park J, Strittmatter S. Chapter 26 Promoting the Regeneration of Axons within the Central Nervous System. 2005, 433-xviii. DOI: 10.1016/b978-012738903-5/50027-8.Peer-Reviewed Original ResearchCentral nervous systemSpinal cord injuryNervous systemPeripheral nervous system axonsPNS Schwann cellsPermanent functional deficitsRegeneration of axonsRegenerative capacityLittle functional recoveryFunctional recoveryCell transplantationCord injuryAxonal regenerationFunctional deficitsPNS neuronsCNS gliaSchwann cellsAxon regenerationCombinatorial treatmentTransplantation studiesPromising targetAxonsKinase inhibitionInjuryProteoglycan digestion
2004
Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury
Li S, Liu BP, Budel S, Li M, Ji B, Walus L, Li W, Jirik A, Rabacchi S, Choi E, Worley D, Sah DW, Pepinsky B, Lee D, Relton J, Strittmatter SM. Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury. Journal Of Neuroscience 2004, 24: 10511-10520. PMID: 15548666, PMCID: PMC6730300, DOI: 10.1523/jneurosci.2828-04.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsEvoked Potentials, MotorFemaleGPI-Linked ProteinsInjections, SpinalMotor ActivityMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNogo ProteinsNogo Receptor 1OligodendrogliaPeptide FragmentsRatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, PeptideRecombinant Fusion ProteinsSerotoninSolubilitySpinal CordSpinal Cord InjuriesConceptsAxonal sproutingTraumatic spinal cord injurySpinal-injured ratsSpinal cord injuryAdult mammalian CNSNogo-66 receptorOligodendrocyte myelin glycoproteinMyelin associated glycoproteinRaphespinal fibersLocomotor recoveryCord injurySpinal injuryMammalian CNSNgR functionTherapeutic potentialAxonal growthNogo-66Myelin glycoproteinInjuryMyelin proteinsImproved locomotionViral blockadeBlockadeFc proteinSproutingNogo-66 Receptor Prevents Raphespinal and Rubrospinal Axon Regeneration and Limits Functional Recovery from Spinal Cord Injury
Kim JE, Liu BP, Park JH, Strittmatter SM. Nogo-66 Receptor Prevents Raphespinal and Rubrospinal Axon Regeneration and Limits Functional Recovery from Spinal Cord Injury. Neuron 2004, 44: 439-451. PMID: 15504325, DOI: 10.1016/j.neuron.2004.10.015.Peer-Reviewed Original ResearchMeSH Keywords5,7-DihydroxytryptamineAnimalsAxonsBehavior, AnimalBlotting, NorthernBlotting, SouthernBrainCell CountCells, CulturedCloning, MolecularCornified Envelope Proline-Rich ProteinsDesipramineDisease Models, AnimalEvoked Potentials, MotorFemaleGanglia, SpinalGlial Fibrillary Acidic ProteinGlucoseGPI-Linked ProteinsGrowth ConesImmunohistochemistryMiceMice, Inbred C57BLMice, KnockoutMotor ActivityMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinNerve RegenerationNeuronsNogo ProteinsNogo Receptor 1Phospholipid EthersProteinsPyramidal TractsReceptors, Cell SurfaceRecovery of FunctionSerotoninSerotonin AgentsSpinal CordSpinal Cord InjuriesTime FactorsConceptsAdult CNSNogo-66Spinal cord injuryAdult mammalian CNSNogo-66 receptorDorsal hemisectionDRG neuronsFunctional recoveryRubrospinal fibersCord injuryMyelin inhibitorsComplete transectionCorticospinal fibersMotor functionSpinal cordMotor impairmentAxon regenerationMammalian CNSAxonal growthAxonal outgrowthCNS myelinMiceInhibitory proteinInjuryGrowth cones
2003
Targeting the Nogo Receptor to Treat Central Nervous System Injuries
Lee DH, Strittmatter SM, Sah DW. Targeting the Nogo Receptor to Treat Central Nervous System Injuries. Nature Reviews Drug Discovery 2003, 2: 872-879. PMID: 14668808, DOI: 10.1038/nrd1228.Peer-Reviewed Original ResearchConceptsCentral nervous systemAxonal regrowthNogo receptorCentral nervous system injuryNovel drug discovery strategyCNS myelinNervous system injurySpinal cord injuryTraumatic head injuryLarge unmet needOligodendrocyte myelin glycoproteinAxonal damageSystem injuryCNS injuryCord injuryAxonal regenerationHead injuryCNS neuronsGrowth cone collapseSuch injuriesAxon regrowthNervous systemUnmet needDrug discovery strategiesInjury