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
Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma
Sekine Y, Kannan R, Wang X, Strittmatter SM. Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma. Experimental Neurology 2022, 353: 114070. PMID: 35398339, PMCID: PMC9555232, DOI: 10.1016/j.expneurol.2022.114070.Peer-Reviewed Original ResearchConceptsAxon regenerationModerate spinal cord contusion injurySpinal cord contusion injuryTraumatic spinal cord injuryAdult mammalian central nervous systemGrowth conesRetinal ganglion cell axonsOptic nerve crushSpinal cord crush injuryGanglion cell axonsSpinal cord injuryMammalian central nervous systemCentral nervous systemCorticospinal axon regenerationContusion injuryAxonal sproutingCrush injuryNerve crushAxonal growth conesCord injuryAxon sproutingCell axonsProximal bodyNervous systemNeural repair
2019
Plexina2 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
2018
Diltiazem Promotes Regenerative Axon Growth
Huebner EA, Budel S, Jiang Z, Omura T, Ho TS, Barrett L, Merkel JS, Pereira LM, Andrews NA, Wang X, Singh B, Kapur K, Costigan M, Strittmatter SM, Woolf CJ. Diltiazem Promotes Regenerative Axon Growth. Molecular Neurobiology 2018, 56: 3948-3957. PMID: 30232777, PMCID: PMC6424671, DOI: 10.1007/s12035-018-1349-5.Peer-Reviewed Original ResearchConceptsL-type calcium channel blockerDorsal root gangliaCentral nervous systemChondroitin sulfate proteoglycanAxon regenerationMouse dorsal root gangliaAdult central nervous systemHuman sensory neuronsCalcium channel blockersSpinal cord injuryRat cortical culturesCord injuryAxonal regrowthRoot gangliaCortical culturesChannel blockersRegenerative propensityRegenerative axon growthSensory neuronsNervous systemPharmacological enhancersAxon growthPermanent lossSulfate proteoglycanAxotomyThe 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 traumaInhibiting poly(ADP-ribosylation) improves axon regeneration
Byrne AB, McWhirter RD, Sekine Y, Strittmatter SM, Miller DM, Hammarlund M. Inhibiting poly(ADP-ribosylation) improves axon regeneration. ELife 2016, 5: e12734. PMID: 27697151, PMCID: PMC5050021, DOI: 10.7554/elife.12734.Peer-Reviewed Original ResearchConceptsNovel intrinsic regulatorAxon regenerationDLK functionChemical inhibitionIntrinsic regulatorRegeneration pathwayPARG expressionIntrinsic regenerative potentialDLK signalingCritical functionsPARGRegenerative potentialPARP inhibitorsProteinPARPMammalian cortical neuronsRegenerationMotor neuronsGABA neuronsPolymeraseCortical neuronsSignalingRegulatorSpeciesNeurons
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 repairGene-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 resultsINPP5F
2011
A 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
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 capacityStrokeIbuprofen 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
2005
Chapter 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
Nogo-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
The Nogo-66 receptor: focusing myelin inhibition of axon regeneration
McGee AW, Strittmatter SM. The Nogo-66 receptor: focusing myelin inhibition of axon regeneration. Trends In Neurosciences 2003, 26: 193-198. PMID: 12689770, DOI: 10.1016/s0166-2236(03)00062-6.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsAxonsCells, CulturedGPI-Linked ProteinsHumansIn Vitro TechniquesMiceMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNerve RegenerationNeural InhibitionNeuronal PlasticityNogo ProteinsNogo Receptor 1RatsReceptor, Nerve Growth FactorReceptors, Cell SurfaceReceptors, Nerve Growth FactorSignal TransductionConceptsNogo-66 receptorMembrane protein NogoSpinal cord injuryFunctional recoveryCord injuryAxonal regrowthSecond messenger pathwaysProtein NogoAdult CNSAxon regenerationMyelin inhibitionAxonal outgrowthAdditional studiesCNS myelinMyelinNeurite elongationPhysiological roleReceptorsMolecular determinantsInhibitorsInhibitionNGRCurrent understanding
2002
Chapter 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
Repulsive factors and axon regeneration in the CNS
Fournier A, Strittmatter S. Repulsive factors and axon regeneration in the CNS. Current Opinion In Neurobiology 2001, 11: 89-94. PMID: 11179877, DOI: 10.1016/s0959-4388(00)00178-1.Peer-Reviewed Original ResearchIdentification 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