Hideyuki Takahashi, PhD
Associate Research ScientistCards
About
Research
Publications
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 activityCharacterizing the Effects of Progranulin Reduction on Tau Pathology and Phenotypes in a Mouse Model of Tauopathy (P4-9.016)
Bhagwagar S, Takahashi H, Strittmatter S. Characterizing the Effects of Progranulin Reduction on Tau Pathology and Phenotypes in a Mouse Model of Tauopathy (P4-9.016). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205227.Peer-Reviewed Original ResearchReduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase
Takahashi H, Bhagwagar S, Nies S, Ye H, Han X, Chiasseu M, Wang G, Mackenzie I, Strittmatter S. Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase. Nature Communications 2024, 15: 1434. PMID: 38365772, PMCID: PMC10873339, DOI: 10.1038/s41467-024-45692-3.Peer-Reviewed Original ResearchConceptsTau inclusionsComorbid proteinopathiesTau aggregation in vitroPromotes tau aggregation in vitroAlzheimer's diseaseProgranulin reductionTDP-43 proteinopathyTauopathy phenotypeTau aggregationAD-tauHuman tauopathiesNeurofibrillary tanglesTauopathy miceReduction of progranulinPurified GlcCerTDP-43Concomitant accumulationAggregation in vitroAssociated with synucleinopathiesNeurodegenerative disordersProteinopathiesGCase inhibitionTauGCaseGlcCer
2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1qAn 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
2021
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells
Franjic D, Skarica M, Ma S, Arellano JI, Tebbenkamp ATN, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Zhang S, Liu Y, Spurrier J, Zhang L, Gudelj I, Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 2021, 110: 452-469.e14. PMID: 34798047, PMCID: PMC8813897, DOI: 10.1016/j.neuron.2021.10.036.Peer-Reviewed Original ResearchConceptsDisease-related proteinsCellular diversityCross-species analysisSingle-nucleus transcriptomesLipid droplet proteinsSpecies-specific propertiesImmature neuron populationTranscriptomic taxonomyAlzheimer's disease-related proteinsEndoplasmic reticulumCell typesHuman neuronsSpecies differencesHistologic signatureNeurogenic capabilityProteinExcitatory neuronsDiversityAdult miceGranule cellsAlzheimer's diseaseNeuron populationsCognitive functionEntorhinal cellsAdult humansSpreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β
Nies SH, Takahashi H, Herber CS, Huttner A, Chase A, Strittmatter SM. Spreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β. Journal Of Biological Chemistry 2021, 297: 101159. PMID: 34480901, PMCID: PMC8477193, DOI: 10.1016/j.jbc.2021.101159.Peer-Reviewed Original ResearchConceptsTau seedsAlzheimer's diseaseAD model miceWT mouse brainPathological tauSynaptic lossTau accumulationWT miceMouse tauTau pathologyTau burdenModel miceTau inclusionsPharmacological interventionsAD riskCognitive declineMouse brainTau aggregatesPyk2 kinaseKnowledge of factorsKinase inhibitorsMiceFyn kinase inhibitorAβMouse aging
2020
Fronto-temporal dementia risk gene TMEM106B has opposing effects in different lysosomal storage disorders
Perez-Canamas A, Takahashi H, Lindborg JA, Strittmatter SM. Fronto-temporal dementia risk gene TMEM106B has opposing effects in different lysosomal storage disorders. Brain Communications 2020, 3: fcaa200. PMID: 33796852, PMCID: PMC7990118, DOI: 10.1093/braincomms/fcaa200.Peer-Reviewed Original ResearchNeuronal ceroid lipofuscinosisLysosomal compartmentGenome-wide association studiesCeroid lipofuscinosisGaucher diseaseLysosomal storage disorderEndo-lysosomal compartmentsTransmembrane proteinStorage disorderVacuolar ATPaseNull phenotypeATPase stateFrontotemporal lobar degenerationAssociation studiesConduritol B epoxidePurkinje cell degenerationLysosomal acidificationMouse phenotypeNeurodegenerative lysosomal diseaseDifferent lysosomal storage disordersTMEM106BNeuronal lossMotor deficitsNeuronal degenerationPhenotypeFyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy
Tang SJ, Fesharaki-Zadeh A, Takahashi H, Nies SH, Smith LM, Luo A, Chyung A, Chiasseu M, Strittmatter SM. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathologica Communications 2020, 8: 96. PMID: 32611392, PMCID: PMC7329553, DOI: 10.1186/s40478-020-00976-9.Peer-Reviewed Original ResearchConceptsRepetitive closed head injuriesMemory deficitsPhospho-tau accumulationChronic variable stressPersistent memory deficitsP301S transgenic miceClosed head injuryFyn inhibitionPassive avoidance learningFyn kinaseGlial activationPhospho-tauPresynaptic markersSynapse lossTau accumulationHead injurySynapse densityPhosphorylated tauTherapeutic benefitTransgenic miceBehavioral improvementTrauma modelTauopathiesSpatial memoryAvoidance learning
2019
Rescue of Transgenic Alzheimer’s Pathophysiology by Polymeric Cellular Prion Protein Antagonists
Gunther EC, Smith LM, Kostylev MA, Cox TO, Kaufman AC, Lee S, Folta-Stogniew E, Maynard GD, Um JW, Stagi M, Heiss JK, Stoner A, Noble GP, Takahashi H, Haas LT, Schneekloth JS, Merkel J, Teran C, Naderi Z, Supattapone S, Strittmatter SM. Rescue of Transgenic Alzheimer’s Pathophysiology by Polymeric Cellular Prion Protein Antagonists. Cell Reports 2019, 26: 145-158.e8. PMID: 30605671, PMCID: PMC6358723, DOI: 10.1016/j.celrep.2018.12.021.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseOligomeric β-amyloid peptideAPPswe/PS1ΔE9 transgenic miceEffective brain concentrationsPotential therapeutic approachΒ-amyloid peptideBrain concentrationsSynapse lossTherapeutic approachesAlzheimer's pathophysiologyTransgenic miceScN2a cellsMemory deficitsCellular prion proteinPathophysiologyTransmissible spongiformAβOsProtein antagonistLow nanomolar affinityDiseasePrPPrion proteinNanomolar affinitySupAntagonist