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 targetingTMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury
Shafit-Zagardo B, Sidoli S, Goldman J, DuBois J, Corboy J, Strittmatter S, Guzik H, Edema U, Arackal A, Botbol Y, Merheb E, Nagra R, Graff S. TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury. Cells 2023, 12: 1734. PMID: 37443768, PMCID: PMC10340176, DOI: 10.3390/cells12131734.Peer-Reviewed Original ResearchConceptsAxonal damageMultiple sclerosisRelapsing-remitting multiple sclerosisHypomorphic miceExperimental autoimmune encephalomyelitisRelapsing-remitting MSNormal-appearing white matterMultiple sclerosis plaquesWhite matter plaquesNon-neurologic controlsWild-type miceBrains of individualsLipid droplet accumulationAutoimmune encephalomyelitisMyelin oligodendrocyteCNS injuryLipid clearanceSpinal cordNeuronal integrityTransmembrane protein 106BWhite matterAlzheimer's diseaseMice resultsDroplet accumulationPlaques
2018
The 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 expressionORL1Functional 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
2016
Inhibition of Poly-ADP-Ribosylation Fails to Increase Axonal Regeneration or Improve Functional Recovery after Adult Mammalian CNS Injury
Wang X, Sekine Y, Byrne AB, Cafferty WB, Hammarlund M, Strittmatter SM. Inhibition of Poly-ADP-Ribosylation Fails to Increase Axonal Regeneration or Improve Functional Recovery after Adult Mammalian CNS Injury. ENeuro 2016, 3: eneuro.0270-16.2016. PMID: 28032120, PMCID: PMC5187389, DOI: 10.1523/eneuro.0270-16.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBenzimidazolesCells, CulturedCerebral CortexDisease Models, AnimalFemaleIsoenzymesMaleMice, 129 StrainMice, Inbred C57BLMice, TransgenicMotor ActivityNerve RegenerationOptic Nerve InjuriesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsRecovery of FunctionSpinal Cord InjuriesThoracic VertebraeConceptsOptic nerve crush injuryNerve crush injuryThoracic spinal cordAxonal regenerationSpinal cordDorsal hemisectionCrush injuryFunctional recoveryPARP inhibitorsMotor function recoveryRecovery of functionPoly (ADP-ribose) polymeraseClinical PARP inhibitorsNeurological recoveryShort hairpin RNACNS traumaCNS injuryFunction recoveryAxonal regrowthSystemic administrationPharmacodynamic actionAxon regenerationTraumatic damageTherapeutic efficacyNeurological trauma
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 injuryPlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition
Shim SO, Cafferty WB, Schmidt EC, Kim BG, Fujisawa H, Strittmatter SM. PlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition. Molecular And Cellular Neuroscience 2012, 50: 193-200. PMID: 22564823, PMCID: PMC3383336, DOI: 10.1016/j.mcn.2012.04.007.Peer-Reviewed Original ResearchConceptsAxonal growthSpinal cordPellet retrieval taskCervical spinal cordWild-type miceContralateral gray matterAxon guidance cuesSevered fibersSprouted fibersAxonal sproutingCorticofugal projectionsFunctional recoveryBehavioral recoveryCNS injuryImpaired forelimbClass 3 semaphorinsCorticospinal fibersCorticospinal tractMedullary pyramidsSynaptic punctaInhibitor receptorsType miceUnilateral pyramidotomyNeuron inhibitionAdult traumaMyelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury
Duffy P, Wang X, Siegel CS, Tu N, Henkemeyer M, Cafferty WB, Strittmatter SM. Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5063-5068. PMID: 22411787, PMCID: PMC3323955, DOI: 10.1073/pnas.1113953109.Peer-Reviewed Original ResearchConceptsAxonal regenerationAxonal growthAdult mammalian central nervous systemAdult CNS injuryDorsal hemisection injurySpinal cord injuryMammalian central nervous systemWild-type miceCentral nervous systemCaudal spinal cordAxonal guidance cuesAxonal growth inhibitionLater time pointsGreater spasticityCNS traumaHemisection injuryCrush siteOptic nerveNeurological functionCNS injuryCord injuryTransection modelGrowth restrictionSpinal cordTraumatic injurySmall-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury
Kopp MA, Liebscher T, Niedeggen A, Laufer S, Brommer B, Jungehulsing GJ, Strittmatter SM, Dirnagl U, Schwab JM. Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury. Cell And Tissue Research 2012, 349: 119-132. PMID: 22350947, PMCID: PMC3744771, DOI: 10.1007/s00441-012-1334-7.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCentral nervous systemAxonal plasticityCord injuryAcute spinal cord injuryExperimental spinal cord injuryNon-steroid anti-inflammatory drugsRelevant SCI modelGrowth-inhibitory environmentCNS injury modelsAnti-inflammatory drugsOligodendrocyte myelin glycoproteinRhoA inhibitionRepulsive guidance moleculeMotor recoveryAxonal sproutingPreclinical evidenceFunctional recoveryLocomotor recoverySCI modelChondroitin sulfate proteoglycanCNS injuryNeurofunctional outcomeGrowth cone collapsePossible clinical translation
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
2007
Functional 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
Extracellular regulators of axonal growth in the adult central nervous system
Liu BP, Cafferty WB, Budel SO, Strittmatter SM. Extracellular regulators of axonal growth in the adult central nervous system. Philosophical Transactions Of The Royal Society B Biological Sciences 2006, 361: 1593-1610. PMID: 16939977, PMCID: PMC1664666, DOI: 10.1098/rstb.2006.1891.Peer-Reviewed Original ResearchConceptsAxonal growth inhibitorsAxonal sproutingCNS injuryAdult CNSAxonal growthAdult central nervous systemAdult CNS injuryCentral nervous system functionRecovery of functionRobust axonal growthAstroglial scar formationAdult CNS axonsCentral nervous systemOligodendrocyte myelin glycoproteinNervous system functionNeurological functionPathological damageAxonal stabilityNervous systemScar formationAxonal receptorsNeuronal connectivityCNS axonsEphrin-B3Such interventions
2005
Nogo-A Interacts with the Nogo-66 Receptor through Multiple Sites to Create an Isoform-Selective Subnanomolar Agonist
Hu F, Liu BP, Budel S, Liao J, Chin J, Fournier A, Strittmatter SM. Nogo-A Interacts with the Nogo-66 Receptor through Multiple Sites to Create an Isoform-Selective Subnanomolar Agonist. Journal Of Neuroscience 2005, 25: 5298-5304. PMID: 15930377, PMCID: PMC2855126, DOI: 10.1523/jneurosci.5235-04.2005.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsAxonsBinding SitesCell LineChick EmbryoChlorocebus aethiopsGlutathione TransferaseGPI-Linked ProteinsHumansIn Vitro TechniquesLigandsMiceMyelin ProteinsNogo ProteinsNogo Receptor 1PeptidesProtein IsoformsProtein Structure, TertiaryReceptors, Cell SurfaceRecombinant Fusion Proteins
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
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 PhospholipasesNogo-66 receptor antagonist peptide promotes axonal regeneration
GrandPré T, Li S, Strittmatter SM. Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 2002, 417: 547-551. PMID: 12037567, DOI: 10.1038/417547a.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsBinding, CompetitiveCentral Nervous SystemCulture Media, ConditionedFemaleGPI-Linked ProteinsGrowth ConesMolecular Sequence DataMotor ActivityMyelin ProteinsMyelin SheathNerve RegenerationNeuritesNogo Receptor 1Peptide FragmentsProtein Structure, TertiaryRatsRats, Sprague-DawleyReceptors, Cell SurfaceSpinal Cord InjuriesConceptsCentral nervous systemAxonal regenerationNogo-66NEP1-40Antagonist peptideAxonal outgrowthNogo-66 receptorPotential therapeutic agentCorticospinal tract regenerationAxonal outgrowth inhibitionCNS myelin inhibitionSignificant axon growthIntrathecal administrationFunctional recoveryCNS injuryCorticospinal tractOutgrowth inhibitorCompetitive antagonistNervous systemMyelin inhibitionTherapeutic agentsAxon growthMonoclonal antibodiesAdult mammalsNogoChapter 25 Nogo and the Nogo-66 receptor
Fournier AE, GrandPré T, Gould G, Wang X, Strittmatter SM. Chapter 25 Nogo and the Nogo-66 receptor. Progress In Brain Research 2002, 137: 361-369. PMID: 12440378, DOI: 10.1016/s0079-6123(02)37027-4.Peer-Reviewed Original ResearchConceptsNogo-66 receptorAxonal regenerationNogo-66Oligodendrocyte myelin glycoproteinAxonal inhibitionAdult vertebrate CNSUnresponsive neuronsChondroitin sulfate proteoglycanCentral nervous system myelinCNS injuryReceptor expressionAxon regenerationMyelin inhibitionMyelin glycoproteinReceptor componentsNogoReceptorsSystem myelinAxonal surfaceSulfate proteoglycanNeuronsInhibitionMyelinVertebrate CNSHigh affinity
2001
Nogo: A Molecular Determinant of Axonal Growth and Regeneration
Grandpré T, Strittmatter S. Nogo: A Molecular Determinant of Axonal Growth and Regeneration. The Neuroscientist 2001, 7: 377-386. PMID: 11597097, DOI: 10.1177/107385840100700507.Peer-Reviewed Original ResearchConceptsCentral nervous systemCNS environmentNervous systemAdult mammalian central nervous systemEnhanced axonal regenerationPersistent functional deficitsMammalian central nervous systemPeripheral nervous systemNeurite outgrowth inhibitorIntegral membrane proteinsCNS traumaFunctional recoveryReactive astrocytesVivo neutralizationCNS injuryAxonal regenerationFunctional deficitsGlial scarNonpermissive natureOutgrowth inhibitorCNS axonsAxonal growthAxonal elongationMembrane proteinsAxon elongationIdentification of a receptor mediating Nogo-66 inhibition of axonal regeneration
Fournier A, GrandPre T, Strittmatter S. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001, 409: 341-346. PMID: 11201742, DOI: 10.1038/35053072.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsAxonsBinding SitesCell DivisionCell LineChickensCloning, MolecularCOS CellsDNA, ComplementaryGene ExpressionGPI-Linked ProteinsGrowth ConesHumansMiceMolecular Sequence DataMyelin ProteinsNerve RegenerationNogo ProteinsNogo Receptor 1Protein Structure, TertiaryReceptors, Cell SurfaceRecombinant Fusion ProteinsConceptsNogo-66Axonal regenerationHuman CNS injuryNogo-66 receptorAxonal inhibitionAdult vertebrate CNSUnresponsive neuronsCentral nervous system myelinCNS injuryReceptor expressionAxon regenerationEnhanced recoveryGlycophosphatidylinositol-linked proteinAxonal extensionNogoNeuronsReceptorsSystem myelinAxonal surfaceInhibitionCell typesVertebrate CNSExtracellular domainHigh affinityCell morphology