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 screen
2021
Optic nerve regeneration screen identifies multiple genes restricting adult neural repair
Lindborg JA, Tran NM, Chenette DM, DeLuca K, Foli Y, Kannan R, Sekine Y, Wang X, Wollan M, Kim IJ, Sanes JR, Strittmatter SM. Optic nerve regeneration screen identifies multiple genes restricting adult neural repair. Cell Reports 2021, 34: 108777. PMID: 33657370, PMCID: PMC8009559, DOI: 10.1016/j.celrep.2021.108777.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCRISPR-Cas SystemsDependovirusFemaleGene EditingGene Expression RegulationGenetic Association StudiesHEK293 CellsHumansInterleukinsMaleMAP Kinase Kinase KinasesMice, Inbred C57BLMice, TransgenicNerve RegenerationNeurogenesisOptic NerveOptic Nerve InjuriesRetinal Ganglion CellsSignal TransductionSTAT3 Transcription FactorConceptsOptic nerve crushRetinal ganglion cellsRegeneration-associated genesShort hairpin RNAIL-22Neural repairCentral nervous system traumaNeurological deficits persistNervous system traumaNerve crushAxonal damageAxonal regenerationGanglion cellsSystem traumaInflammatory responseCNS regenerationDeficits persistAxonal growthHairpin RNAConcurrent activationTranscription 3Cell-autonomous factorsKinase pathwaySignal transducerRepair
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 neuronsProtein
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
2017
Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS
Hirokawa T, Zou Y, Kurihara Y, Jiang Z, Sakakibara Y, Ito H, Funakoshi K, Kawahara N, Goshima Y, Strittmatter SM, Takei K. Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS. Scientific Reports 2017, 7: 12119. PMID: 28935984, PMCID: PMC5608707, DOI: 10.1038/s41598-017-12449-6.Peer-Reviewed Original ResearchConceptsSpinal cord injuryOptic nerve crushAxonal regenerationMotor recoveryNerve crushNeural repairRetinal ganglion cell axonal regenerationAdult mammalian central nervous systemIntrinsic motor recoverySpontaneous neural repairAxonal growth inhibitorsMammalian central nervous systemCentral nervous systemNon-permissive environmentLevel of functionUntreated miceFunctional recoveryCord injuryReceptor antagonistNeuronal overexpressionNervous systemGenetic deletionViral overexpressionCrushInhibitors
2016
Rewiring the spinal cord: Direct and indirect strategies
Dell’Anno M, Strittmatter SM. Rewiring the spinal cord: Direct and indirect strategies. Neuroscience Letters 2016, 652: 25-34. PMID: 28007647, PMCID: PMC5466898, DOI: 10.1016/j.neulet.2016.12.002.Peer-Reviewed Original ResearchConceptsSpinal cordNeural stem cellsNeural stem cell-derived neuronsTransplanted neural stem cellsNeural stem cell transplantationAdult central nervous systemLong-distance axonsNeutralization of myelinRecipient spinal cordStem cell transplantationSpinal cord injuryStem cell-derived neuronsCentral nervous systemCell-derived neuronsIntrinsic regenerative capacityPoor intrinsic regenerative capacityStem cellsNeurologic recoveryAxonal sproutingSecondary complicationsCell transplantationCord injuryAxonal regenerationGlial cellsAdult brainInhibition 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
2015
Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury
Zou Y, Stagi M, Wang X, Yigitkanli K, Siegel CS, Nakatsu F, Cafferty WB, Strittmatter SM. Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury. Journal Of Neuroscience 2015, 35: 10429-10439. PMID: 26203138, PMCID: PMC4510284, DOI: 10.1523/jneurosci.1718-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsDisease Models, AnimalGene Knockdown TechniquesImmunohistochemistryInositol Polyphosphate 5-PhosphatasesMiceMice, Inbred C57BLMice, KnockoutNerve RegenerationPhosphoric Monoester HydrolasesRecovery of FunctionReverse Transcriptase Polymerase Chain ReactionSpinal Cord InjuriesConceptsSpinal cord injuryCord injuryEndogenous suppressorAxon regenerationNonoverlapping substrate specificityGenome-wide scaleHigh-throughput functional screensFunctional recoveryAxonal regenerationCNS axon repairSpinal cord injury researchDorsal hemisection injuryMammalian genesPI3K/AKT/mTOR pathwayCNS axon growthAKT/mTOR pathwayLipid phosphataseCorticospinal tract axonsCNS axon regenerationAdult mammalian CNSFunctional screenSubstrate specificityNovel suppressorShRNA resultsINPP5FIntravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma
Wang X, Lin J, Arzeno A, Choi JY, Boccio J, Frieden E, Bhargava A, Maynard G, Tsai JC, Strittmatter SM. Intravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma. Investigative Ophthalmology & Visual Science 2015, 56: 1357-1366. PMID: 25655801, PMCID: PMC4338631, DOI: 10.1167/iovs.14-15472.Peer-Reviewed Original ResearchConceptsOptic nerve crushFluro-GoldNerve crushAxonal regenerationGanglion cellsOptic nerve crush injuryRetinal ganglion cell degenerationRGC axonal regenerationNerve crush injuryDisease-modifying therapiesGanglion cell degenerationDecoy proteinMicrobead modelVitreal spaceIntravitreal treatmentRGC densityAxonal sproutingCrush injuryGlaucoma modelNeuroprotective effectsAnterior chamberControl ratsVision lossAnterograde labelingBolus administration
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 injuryMyelin-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 injury
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
2009
Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth
Wang X, Budel S, Baughman K, Gould G, Song KH, Strittmatter SM. Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth. Journal Of Neurotrauma 2009, 26: 81-95. PMID: 19125588, PMCID: PMC2913782, DOI: 10.1089/neu.2007.0464.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory Agents, Non-SteroidalAxotomyChick EmbryoDisease Models, AnimalEfferent PathwaysFemaleGrowth ConesGrowth InhibitorsIbuprofenMiceNerve RegenerationNIH 3T3 CellsPyramidal TractsRaphe NucleiRatsRats, Sprague-DawleyRhoA GTP-Binding ProteinSpinal CordSpinal Cord InjuriesConceptsSpinal cord injuryAxonal sproutingCord injuryAxonal regenerationAxon regenerationNonsteroidal anti-inflammatory drugsComplete spinal cord transectionWeight-bearing statusSpinal cord contusionRecovery of ratsSpinal cord traumaTreatment of miceAdministration of ibuprofenSpinal cord transectionAnti-inflammatory drugsCorticospinal axon regenerationAction of ibuprofenRaphespinal axonsSpinal contusionCord contusionCord traumaMicroglial reactionChondroitin sulfate proteoglycanCord transectionCorticospinal fibers
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
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 SurfaceRegenerationAxonal 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
Experience-Driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor
McGee AW, Yang Y, Fischer QS, Daw NW, Strittmatter SM. Experience-Driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor. Science 2005, 309: 2222-2226. PMID: 16195464, PMCID: PMC2856689, DOI: 10.1126/science.1114362.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChondroitin Sulfate ProteoglycansDarknessDominance, OcularElectrophysiologyGamma-Aminobutyric AcidGene TargetingGPI-Linked ProteinsMiceMice, Inbred C57BLMutationMyelin Basic ProteinMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinNeuritesNeuronal PlasticityNeuronsNogo ProteinsNogo Receptor 1Photic StimulationReceptors, Cell SurfaceSignal TransductionVisual CortexConceptsOcular dominanceOcular dominance plasticityNogo-66 receptorExperience-dependent plasticityPostnatal critical periodCritical periodFunctional recoveryAxonal regenerationMonocular deprivationNogo receptorDays postnatalVisual cortexNeural circuitryPathological traumaJuvenile ageMyelinReceptorsNGRPlasticityPostnatalCortexOMgpTraumaNogoCessationEffect of combined treatment with methylprednisolone and soluble Nogo‐66 receptor after rat spinal cord injury
Ji B, Li M, Budel S, Pepinsky RB, Walus L, Engber TM, Strittmatter SM, Relton JK. Effect of combined treatment with methylprednisolone and soluble Nogo‐66 receptor after rat spinal cord injury. European Journal Of Neuroscience 2005, 22: 587-594. PMID: 16101740, PMCID: PMC2846292, DOI: 10.1111/j.1460-9568.2005.04241.x.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAxonsBehavior, AnimalBiotinCells, CulturedChick EmbryoDextransDisease Models, AnimalDose-Response Relationship, DrugDrug InteractionsDrug Therapy, CombinationExploratory BehaviorFemaleGanglia, SpinalGPI-Linked ProteinsImmunoglobulin GLaminectomyMethylprednisoloneMyelin ProteinsMyelin SheathNerve RegenerationNeuronsNogo Receptor 1Pyramidal TractsRatsRats, Long-EvansReceptors, Cell SurfaceReceptors, PeptideRecombinant ProteinsRecovery of FunctionSpinal Cord InjuriesConceptsSpinal cord injuryCord injuryRat spinal cord injuryMP treatmentAdult central nervous systemThoracic dorsal hemisectionNovel experimental therapiesCorticospinal tract axonsRecovery of functionNogo-66 receptorNumber of axonsCentral nervous systemGrowth inhibitory effectsDorsal hemisectionBBB scoresAxonal sproutingFunctional recoveryBresnahan (BBB) scoringAxonal regenerationMotor neuronsExperimental therapiesMethylprednisoloneSynthetic glucocorticoidNervous systemAxonal growthNogo-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