2025
Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior
Jin S, Yoon N, Wei M, Worgall T, Rubinelli L, Horvath T, Min W, Diano N, di Lorenzo A, Diano S. Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior. Cell Metabolism 2025, 37: 1400-1412.e8. PMID: 40334659, PMCID: PMC12136989, DOI: 10.1016/j.cmet.2025.04.005.Peer-Reviewed Original ResearchConceptsAgRP neuron activityNogo-AAgRP neuronsNeuronal activityCeramide levelsNogo-A expressionCellular lipid metabolismIntracellular lipid transportSphingolipid de novo biosynthesisDownregulation of enzymesIncreased ceramide levelsLipid metabolismHigh-fat diet-induced obesityFeeding behaviorAgouti-related proteinControl of feedingControlling lipid metabolismAssociated with brain developmentWhole-body metabolismFatty acid oxidationReticulon 4Food intakeMitochondrial functionSynaptic plasticityLipid transportSuppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disorders
2024
Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage
Gong K, Xue C, Feng Z, Pan R, Wang M, Chen S, Chen Y, Guan Y, Dai L, Zhang S, Jiang L, Li L, Wang B, Yin Z, Ma L, Iwakiri Y, Tang J, Liao C, Chen H, Duan Y. Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage. Nature Communications 2024, 15: 6845. PMID: 39122737, PMCID: PMC11315690, DOI: 10.1038/s41467-024-51352-3.Peer-Reviewed Original ResearchConceptsEnteroendocrine cellsEndoplasmic reticulum (ER)-resident proteinGlucagon-like peptide 1Nogo-BEndoplasmic reticulumStimulate insulin secretionPotential therapeutic targetProglucagonGlucagon-like peptide 1 receptorInhibit glucagon secretionRegulatory processesIntestinal tractProglucagon fragmentInsulin secretionCleavageNogo-B knockoutTherapeutic targetPancreatic cellsPeptide 1Glucagon secretionCellsReticulonGolgiReticulon 4BInsulin resistance
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 targetingThe nanoscale organization of reticulon 4 shapes local endoplasmic reticulum structure in situ
Fuentes L, Marin Z, Tyson J, Baddeley D, Bewersdorf J. The nanoscale organization of reticulon 4 shapes local endoplasmic reticulum structure in situ. Journal Of Cell Biology 2023, 222: e202301112. PMID: 37516910, PMCID: PMC10373298, DOI: 10.1083/jcb.202301112.Peer-Reviewed Original ResearchEndoplasmic ReticulumNogo Proteins
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 localizationResponseCellsInhibition of high-fat diet–induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms
Wang X, Yang Y, Zhao D, Zhang S, Chen Y, Chen Y, Feng K, Li X, Han J, Iwakiri Y, Duan Y, Yang X. Inhibition of high-fat diet–induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms. Journal Of Biological Chemistry 2022, 298: 101561. PMID: 34998825, PMCID: PMC8814669, DOI: 10.1016/j.jbc.2022.101561.Peer-Reviewed Original ResearchConceptsHigh-fat dietMetabolic disordersHigh-fat diet-induced obesityBody mass index valuesInhibition of NogoSerum proinflammatory cytokinesDiet-induced obesityInfiltration of macrophagesType 2 diabetesWT littermate control miceLittermate control miceEffects of NogoMass index valuesBrown adipose tissueProtect miceNormal chowControl miceProinflammatory cytokinesInsulin resistanceObesity treatmentRisk factorsLipid profileCardiovascular diseaseProtein NogoObesity
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
2020
Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity
Zhang S, Guo F, Yu M, Yang X, Yao Z, Li Q, Wei Z, Feng K, Zeng P, Zhao D, Li X, Zhu Y, Miao QR, Iwakiri Y, Chen Y, Han J, Duan Y. Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity. Journal Of Hepatology 2020, 73: 1482-1495. PMID: 32738448, DOI: 10.1016/j.jhep.2020.07.034.Peer-Reviewed Original ResearchConceptsDiet-induced metabolic disordersHepatic lipid accumulationInsulin sensitivityMetabolic disordersInsulin resistanceNogo expressionNon-alcoholic fatty liver diseaseDiet-induced body weight gainInsulin activityDiet-induced glucose intoleranceLipid accumulationFatty liver diseaseHigh-fructose dietGrowth factor 21Littermate control miceDe novo lipogenesisHigh-carbohydrate dietBody weight gainCarbohydrate-responsive element-binding proteinExpression of ChREBPChREBP activityEndoplasmic reticulum stressMetabolic complicationsGlucose intoleranceLiver disease
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 neuronsProteinPoly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver
Cui J, Piotrowski-Daspit AS, Zhang J, Shao M, Bracaglia LG, Utsumi T, Seo YE, DiRito J, Song E, Wu C, Inada A, Tietjen GT, Pober JS, Iwakiri Y, Saltzman WM. Poly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver. Journal Of Controlled Release 2019, 304: 259-267. PMID: 31054286, PMCID: PMC6613984, DOI: 10.1016/j.jconrel.2019.04.044.Peer-Reviewed Original ResearchTowards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs
Le-Niculescu H, Roseberry K, Levey D, Rogers J, Kosary K, Prabha S, Jones T, Judd S, McCormick M, Wessel A, Williams A, Phalen P, Mamdani F, Sequeira A, Kurian S, Niculescu A. Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs. Molecular Psychiatry 2019, 25: 918-938. PMID: 30862937, PMCID: PMC7192849, DOI: 10.1038/s41380-019-0370-z.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultbeta 2-MicroglobulinBiomarkersDEAD-box RNA HelicasesFemaleGene ExpressionHumansMaleMental DisordersMiddle AgedMolecular Targeted TherapyNogo ProteinsPrecision MedicinePredictive Value of TestsProto-Oncogene ProteinsReceptors, ImmunologicStress, PsychologicalTacrolimus Binding ProteinsTelomere HomeostasisConceptsPredictive biomarkersGene expression biomarkersTelomere lengthBlood gene expression biomarkersPossible new drug candidateStress disorderPsychological stressFuture psychiatric hospitalizationsVisual analog scaleHigh-risk groupSimple visual analog scaleDrug repurposing analysisExpression biomarkersGene expression signaturesAnalog scaleAdverse outcomesCalcium folinateCohort designHormonal changesPsychiatric hospitalizationDecreased qualityBiomarker findingsPsychiatric disordersPsychiatric patientsPatient stratificationPlexina2 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
Dynamic nanoscale morphology of the ER surveyed by STED microscopy
Schroeder LK, Barentine AES, Merta H, Schweighofer S, Zhang Y, Baddeley D, Bewersdorf J, Bahmanyar S. Dynamic nanoscale morphology of the ER surveyed by STED microscopy. Journal Of Cell Biology 2018, 218: 83-96. PMID: 30442642, PMCID: PMC6314542, DOI: 10.1083/jcb.201809107.Peer-Reviewed Original Research
2017
An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization
Park J, Shao M, Kim MY, Baik SK, Cho MY, Utsumi T, Satoh A, Ouyang X, Chung C, Iwakiri Y. An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization. Hepatology 2017, 65: 1720-1734. PMID: 28090670, PMCID: PMC5397326, DOI: 10.1002/hep.29051.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseasePositive Kupffer cellsKupffer cellsLiver injuryALD patientsLiver diseaseM1 polarizationKO miceM2 polarizationLieber-DeCarli ethanol liquid dietDisease severityM1/M2 polarizationKupffer cell polarizationEthanol liquid dietHepatic triglyceride levelsM2 macrophage polarizationHigher hepatic triglyceride levelsChronic ethanol feedingNew therapeutic targetsER stressAbsence of NogoM2 statusWT miceM1 activationTriglyceride levels
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
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