2024
Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism
Takahashi H, Perez-Canamas A, Lee C, Ye H, Han X, Strittmatter S. Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism. Communications Biology 2024, 7: 1088. PMID: 39237682, PMCID: PMC11377756, DOI: 10.1038/s42003-024-06810-5.Peer-Reviewed Original ResearchConceptsMyelin lipid metabolismCo-immunoprecipitation assaysSulfated derivative sulfatideLipid metabolismAssociated with multiple neurological disordersCo-immunoprecipitationTMEM106BTransmembrane proteinsAmyloid fibrilsTMEM106B deficiencyHypomyelinating leukodystrophyAlzheimer's diseasePhysiological functionsFrontotemporal dementiaMolecular levelNeurodegenerative brainGalactosylceramidaseLipidomic analysisMultiple neurological disordersMetabolismMyelin lipidsDecreased levelsEndolysosomesAmyloidGalactosylceramidase activity
2022
An unexpected protein aggregate in diseased and ageing brains
Takahashi H, Strittmatter SM. An unexpected protein aggregate in diseased and ageing brains. Nature 2022, 605: 227-228. PMID: 35379977, DOI: 10.1038/d41586-022-00873-2.Peer-Reviewed Original Research
2020
Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging
Sadasivam P, Fang XT, Toyonaga T, Lee S, Xu Y, Zheng MQ, Spurrier J, Huang Y, Strittmatter SM, Carson RE, Cai Z. Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular Imaging And Biology 2020, 23: 372-381. PMID: 33258040, PMCID: PMC8105262, DOI: 10.1007/s11307-020-01567-9.Peer-Reviewed Original ResearchConceptsBrain stemAlzheimer's diseaseMin postinjectionAnimal modelsAPP/PS1 miceReference regionStandardized uptake value ratioDynamic PET imaging dataUptake value ratioRodent brain tissueStatic PET scansDifferent imaging windowsPET imaging dataWild-type controlsReference tissue modelPS1 miceAD pathogenesisTherapeutic effectMouse modelRodent modelsLittermate controlsPET scansRodent brainPreclinical imaging studiesTherapeutic drug efficacyPET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
2019
Anti‐PrPC antibody rescues cognition and synapses in transgenic alzheimer mice
Cox TO, Gunther EC, Brody AH, Chiasseu MT, Stoner A, Smith LM, Haas LT, Hammersley J, Rees G, Dosanjh B, Groves M, Gardener M, Dobson C, Vaughan T, Chessell I, Billinton A, Strittmatter SM. Anti‐PrPC antibody rescues cognition and synapses in transgenic alzheimer mice. Annals Of Clinical And Translational Neurology 2019, 6: 554-574. PMID: 30911579, PMCID: PMC6414488, DOI: 10.1002/acn3.730.Peer-Reviewed Original ResearchConceptsAPP/PS1 transgenic micePS1 transgenic miceBrain antibodiesTransgenic miceDisease pathophysiologyDisease pathologyTransgenic Alzheimer's miceAlzheimer's disease pathologyAlzheimer's disease pathophysiologyHuman monoclonal antibodyPreclinical therapeutic efficacyHigh-affinity receptorAmyloid-beta oligomersLast doseTransgenic brainsPlaque pathologyAlzheimer's micePreclinical dataSynaptic damageAnti-PrPc antibodiesSynaptic densityIntraperitoneal dosingBrain biochemistryCentral synapsesTherapeutic efficacy
2018
Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers
Kostylev MA, Tuttle MD, Lee S, Klein LE, Takahashi H, Cox TO, Gunther EC, Zilm KW, Strittmatter SM. Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers. Molecular Cell 2018, 72: 426-443.e12. PMID: 30401430, PMCID: PMC6226277, DOI: 10.1016/j.molcel.2018.10.009.Peer-Reviewed Original ResearchConceptsAmino-terminal GlyCellular prion proteinProtein phase separationAmyloid-β OligomersPlasma membraneMembraneless organellesAla residuesRecombinant PrPPrion proteinCell surfaceConformation shiftConformational transitionHelical conformationAβ speciesPrPSupSpongiform degenerationEndogenous AβOsOrganellesPrPCSuch domainsSpeciesDomainProteinAβOs
2017
Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease
Salazar SV, Gallardo C, Kaufman AC, Herber CS, Haas LT, Robinson S, Manson JC, Lee MK, Strittmatter SM. Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease. Journal Of Neuroscience 2017, 37: 9207-9221. PMID: 28842420, PMCID: PMC5607466, DOI: 10.1523/jneurosci.0722-17.2017.Peer-Reviewed Original ResearchConceptsDisease onsetAlzheimer's diseaseFamilial Alzheimer's diseaseDisease pathophysiologyCellular prion proteinHippocampal synapse lossSoluble oligomeric amyloidTransgenic Alzheimer's diseaseTime of diagnosisDisease-modifying therapiesAlzheimer's disease pathophysiologyPotential therapeutic targetAD-related phenotypesMonths of ageRole of PrPSymptom onsetSynaptic deficitsPrion proteinSynapse lossCatecholaminergic neuronsPlaque densityBehavioral deficitsOligomeric amyloidMouse modelPresent symptomsLoss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice
Klein ZA, Takahashi H, Ma M, Stagi M, Zhou M, Lam TT, Strittmatter SM. Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice. Neuron 2017, 95: 281-296.e6. PMID: 28728022, PMCID: PMC5558861, DOI: 10.1016/j.neuron.2017.06.026.Peer-Reviewed Original ResearchConceptsLysosomal protein levelsFrontotemporal lobar degenerationProtein levelsMultiple lysosomal enzymesLysosomal enzymesV0 subunitsTMEM106B geneProteomic analysisProgranulin-deficient miceExtent of neurodegenerationCommon neurodegenerative disorderLysosomal acidificationLysosomal enzyme levelsProtein 1Microglial accumulationRisk modificationFTLD riskBehavioral abnormalitiesRetinal degenerationNeurodegenerative disordersFrontotemporal dementiaGRNTMEM106BFunctional relationshipEnzyme levelsSilent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes
Haas LT, Salazar SV, Smith LM, Zhao HR, Cox TO, Herber CS, Degnan AP, Balakrishnan A, Macor JE, Albright CF, Strittmatter SM. Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes. Cell Reports 2017, 20: 76-88. PMID: 28683325, PMCID: PMC5547898, DOI: 10.1016/j.celrep.2017.06.023.Peer-Reviewed Original ResearchConceptsAD transgenic mouse modelDisease pathologyMetabotropic glutamate receptor 5Allosteric modulationGlutamate receptor 5Alzheimer's disease pathologyTransgenic mouse brainSilent allosteric modulatorsTransgenic mouse modelBroad therapeutic windowMouse phenotypeAD interventionSynaptic depletionBrain slicesGlutamate signalingMouse modelTherapeutic windowAD phenotypeReceptor 5Mouse brainAllosteric modulatorsMemory deficitsCellular prion proteinPathological roleMGluR5
2016
Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
Onorati M, Li Z, Liu F, Sousa AMM, Nakagawa N, Li M, Dell’Anno M, Gulden FO, Pochareddy S, Tebbenkamp AT, Han W, Pletikos M, Gao T, Zhu Y, Bichsel C, Varela L, Szigeti-Buck K, Lisgo S, Zhang Y, Testen A, Gao XB, Mlakar J, Popovic M, Flamand M, Strittmatter SM, Kaczmarek LK, Anton ES, Horvath TL, Lindenbach BD, Sestan N. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia. Cell Reports 2016, 16: 2576-2592. PMID: 27568284, PMCID: PMC5135012, DOI: 10.1016/j.celrep.2016.08.038.Peer-Reviewed Original ResearchMeSH KeywordsAxl Receptor Tyrosine KinaseBrainCell DeathCentrosomeFetusGene Expression ProfilingHumansImmunity, InnateMicrocephalyMitochondriaMitosisNeocortexNeural Stem CellsNeuroepithelial CellsNeurogliaNeuronsNeuroprotective AgentsNucleosidesPhosphorylationProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSpinal CordTranscription, GeneticVirus ReplicationZika VirusZika Virus InfectionConceptsRadial glial cellsNES cellsNeuroepithelial stem cellsZIKV infectionFetal brain slicesStem cellsEarly human neurodevelopmentHuman neuroepithelial stem cellsHuman neural stem cellsCell deathSingle-cell RNA-seqNeural stem cellsNeurodevelopment defectsZIKV replicationGlial cellsBrain slicesPotential treatmentRadial gliaZika virusPhospho-TBK1Neurodevelopmental defectsRNA-seqSupernumerary centrosomesNucleoside analoguesHuman neurodevelopment
2015
Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood
Bhagat SM, Butler SS, Taylor JR, McEwen BS, Strittmatter SM. Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood. Molecular Psychiatry 2015, 21: 1281-1289. PMID: 26619810, PMCID: PMC4887429, DOI: 10.1038/mp.2015.179.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderExtinction trainingFear memorySpontaneous fear recoveryBasolateral amygdalaJuvenile rodentsFear recoveryFear renewalFear extinctionFear expressionInhibitory synapse markersNgR1 expressionStress disorderNogo receptor 1Anxiety disordersInfralimbic cortexCritical periodNeural plasticityMemoryTemporary windowsReceptor 1TrainingAdulthoodNgR1 functionNaive mice
2013
Anatomical Plasticity of Adult Brain Is Titrated by Nogo Receptor 1
Akbik FV, Bhagat SM, Patel PR, Cafferty WB, Strittmatter SM. Anatomical Plasticity of Adult Brain Is Titrated by Nogo Receptor 1. Neuron 2013, 77: 859-866. PMID: 23473316, PMCID: PMC3594793, DOI: 10.1016/j.neuron.2012.12.027.Peer-Reviewed Original ResearchConceptsNgr1-/- miceNogo receptor 1Somatosensory cortexReceptor 1Adult cerebral cortexDendritic spine turnoverDendritic spine dynamicsAnatomical plasticityCerebral cortexControl miceSpine turnoverAxonal varicositiesWhisker removalAdult brainDendritic spinesSpine dynamicsNull miceAge 26Synaptic turnoverAnatomical connectivityConditional deletionMiceLower set pointNgR1CortexAmyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease
Um JW, Strittmatter SM. Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease. Prion 2013, 7: 37-41. PMID: 22987042, PMCID: PMC3609048, DOI: 10.4161/pri.22212.Peer-Reviewed Original ResearchConceptsCellular prion proteinPrion proteinSignal transduction downstreamTransduction downstreamAlzheimer's diseaseFyn kinaseFunctional consequencesAβ oligomersAmyloid-β OligomersNeuronal surfaceHigh-affinity receptorOligomer complexesAD-related phenotypesCentral roleProteinAD pathogenesisRecent evidencePrevalent causeTherapeutic interventionsFynKinaseOligomersPhenotypeDiseaseDownstream
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
Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein
Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Laurén J, Gimbel ZA, Strittmatter SM. Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein. Journal Of Neuroscience 2010, 30: 6367-6374. PMID: 20445063, PMCID: PMC3323924, DOI: 10.1523/jneurosci.0395-10.2010.Peer-Reviewed Original ResearchConceptsTransgenic miceAlzheimer's diseaseCellular prion proteinSpatial learningAD transgenic miceTransgenic AD modelTransgenic Alzheimer's micePrnp-/- miceAD-related phenotypesAmyloid-beta peptideAbeta accumulationAbeta plaquesAbeta levelsAD micePrion proteinAlzheimer's miceAxonal degenerationAPP expressionSynaptic markersHippocampal slicesDetectable impairmentEarly deathAD modelBehavioral impairmentsMemory impairment
2009
β-amyloid oligomers and cellular prion protein in Alzheimer’s disease
Gunther EC, Strittmatter SM. β-amyloid oligomers and cellular prion protein in Alzheimer’s disease. Journal Of Molecular Medicine 2009, 88: 331-338. PMID: 19960174, PMCID: PMC2846635, DOI: 10.1007/s00109-009-0568-7.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseAβ oligomersDisease pathophysiologyCellular prion proteinProgression of ADAlzheimer's disease pathophysiologyΒ-amyloid oligomersΒ-amyloid peptidePrion proteinBrain slicesAlzheimer's diseaseSynaptic functionFunctional receptorsNeurodegenerative diseasesDiseasePotential mediatorsAβ assembliesReceptorsAβ monomersPrPCPathophysiologyNeurotoxicityPlaquesProgressionLGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology
Owuor K, Harel NY, Englot DJ, Hisama F, Blumenfeld H, Strittmatter SM. LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. Molecular And Cellular Neuroscience 2009, 42: 448-457. PMID: 19796686, PMCID: PMC2783222, DOI: 10.1016/j.mcn.2009.09.008.Peer-Reviewed Original ResearchConceptsNeuronal morphologyAutosomal dominant partial epilepsyCA1 pyramidal neuronsSeizure thresholdSpontaneous seizuresPartial epilepsyPyramidal neuronsDendritic arborizationLGI1PSD-95LGI1 geneEpilepsy genesADAM23ADPEAFADAM22EpilepsyNeurite outgrowthIon channelsBrain genesUnbiased screenAuditory featuresOutgrowthSeizuresArborizationRelated proteins
2008
Genetic Variants of Nogo-66 Receptor with Possible Association to Schizophrenia Block Myelin Inhibition of Axon Growth
Budel S, Padukkavidana T, Liu BP, Feng Z, Hu F, Johnson S, Lauren J, Park JH, McGee AW, Liao J, Stillman A, Kim JE, Yang BZ, Sodi S, Gelernter J, Zhao H, Hisama F, Arnsten AF, Strittmatter SM. Genetic Variants of Nogo-66 Receptor with Possible Association to Schizophrenia Block Myelin Inhibition of Axon Growth. Journal Of Neuroscience 2008, 28: 13161-13172. PMID: 19052207, PMCID: PMC2892845, DOI: 10.1523/jneurosci.3828-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChick EmbryoChlorocebus aethiopsChromosome MappingCodonCOS CellsFemaleGenetic Predisposition to DiseaseGPI-Linked ProteinsGrowth ConesGrowth InhibitorsHumansMaleMiceMice, KnockoutMutationMyelin ProteinsNerve Fibers, MyelinatedNeurogenesisNeuronal PlasticityNogo Receptor 1Organ Culture TechniquesRatsReceptors, Cell SurfaceSchizophreniaConceptsMyelin inhibitionNogo-66 receptorCase-control analysisMyelin-specific genesAxonal sproutingMyelin signalGenetic predispositionAxon inhibitionNeuronal culturesPossible associationReceptor 1Disease riskAxon growthSchizophreniaAxonal proteinsPotential endophenotypeMemory functionGenetic variantsDysfunctional proteinsInhibitionSchizophrenia susceptibilityDominant negativeProtein exhibitCandidate genesChromosome 22q11
2007
Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice.
Park JH, Strittmatter SM. Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice. Current Alzheimer Research 2007, 4: 568-70. PMID: 18220524, PMCID: PMC2846284, DOI: 10.2174/156720507783018235.Peer-Reviewed Original ResearchConceptsTransgenic miceAlzheimer's diseasePlaque depositionAdult central nervous systemAlzheimer's transgenic miceNogo-66 receptorAmyloid β plaquesCentral nervous systemAxonal sproutingAβ accumulationΒ plaquesDystrophic neuritesPathologic changesNogo receptorNervous systemBrain APPDiseasePotential mechanistic basisMiceExpression increasesNGR modificationReceptorsNeurite responseNGRMechanistic basisLRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia
Francks C, Maegawa S, Laurén J, Abrahams BS, Velayos-Baeza A, Medland SE, Colella S, Groszer M, McAuley EZ, Caffrey TM, Timmusk T, Pruunsild P, Koppel I, Lind PA, Matsumoto-Itaba N, Nicod J, Xiong L, Joober R, Enard W, Krinsky B, Nanba E, Richardson AJ, Riley BP, Martin NG, Strittmatter SM, Möller HJ, Rujescu D, St Clair D, Muglia P, Roos JL, Fisher SE, Wade-Martins R, Rouleau GA, Stein JF, Karayiorgou M, Geschwind DH, Ragoussis J, Kendler KS, Airaksinen MS, Oshimura M, DeLisi LE, Monaco AP. LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. Molecular Psychiatry 2007, 12: 1129-1139. PMID: 17667961, PMCID: PMC2990633, DOI: 10.1038/sj.mp.4002053.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCell Line, TransformedChromosomes, Human, Pair 2Family HealthFemaleFunctional LateralityGene Expression Regulation, DevelopmentalGenetic Predisposition to DiseaseGenotypeHumansIn Situ HybridizationKaryotypingMaleMembrane ProteinsMiceNerve Tissue ProteinsSchizophreniaSubcellular FractionsConceptsHuman brain asymmetryPutative genetic effectsEvolutionary originImprinted genesChromosome 2p12Candidate genesBehavioral evolutionHuman handednessNeuronal differentiationBrain asymmetryLRRTM1Specific forebrain structuresSchizophrenia/schizoaffective disorderGenetic effectsGenesSame haplotypePotential genetic influencesDirect confirmatory evidenceCommon neurodevelopmental disorderFunction underliesForebrain structuresSchizoaffective disorderHaplotypesSignificant associationNeuropsychiatric disorders