2023
Neuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein
Stoner A, Fu L, Nicholson L, Zheng C, Toyonaga T, Spurrier J, Laird W, Cai Z, Strittmatter S. Neuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein. Alzheimer's Research & Therapy 2023, 15: 201. PMID: 37968719, PMCID: PMC10647125, DOI: 10.1186/s13195-023-01345-z.Peer-Reviewed Original ResearchConceptsSynapse lossDKI miceTau accumulationBrain immune activationNeural network dysfunctionPhospho-tau accumulationAccumulation of tauNeuronal genesInflammatory markersAD miceAβ levelsPrion proteinDystrophic neuritesImmune activationTau pathologyNeuronal gene expressionAmyloid-β OligomersGliotic reactionNetwork dysfunctionBehavioral deficitsSynaptic failureAD modelMemory impairmentAlzheimer's diseaseFunction of age
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
Silent 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
2015
Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease
Haas LT, Salazar SV, Kostylev MA, Um JW, Kaufman AC, Strittmatter SM. Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease. Brain 2015, 139: 526-546. PMID: 26667279, PMCID: PMC4840505, DOI: 10.1093/brain/awv356.Peer-Reviewed Original ResearchConceptsCellular prion proteinDisease-related phenotypesPrion proteinMetabotropic glutamate receptor 5Glutamate receptor 5Protein tyrosine kinase 2 betaCalmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IIProtein kinase IIReceptor 5Protein associatesGenetic interactionsObligate complexesGenetic couplingDisease pathogenesisDisease pathologyKinase IIIntracellular proteinsAlzheimer's disease-related phenotypesSingle heterozygotesProteinBiochemical evidenceProtein mediatorsDisease-modifying interventionsTransgenic model micePrion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models*
Kostylev MA, Kaufman AC, Nygaard HB, Patel P, Haas LT, Gunther EC, Vortmeyer A, Strittmatter SM. Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models*. Journal Of Biological Chemistry 2015, 290: 17415-17438. PMID: 26018073, PMCID: PMC4498078, DOI: 10.1074/jbc.m115.643577.Peer-Reviewed Original ResearchAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBehavior, AnimalDisease Models, AnimalFemaleHumansMaleMemory DisordersMiceMice, Inbred C57BLMice, Mutant StrainsMice, TransgenicMiddle AgedMolecular WeightPrefrontal CortexPresenilin-1PrionsProtein Structure, QuaternaryPrPC ProteinsRecombinant Proteins
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 monomersPrPCPathophysiologyNeurotoxicityPlaquesProgressionCellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature 2009, 457: 1128-1132. PMID: 19242475, PMCID: PMC2748841, DOI: 10.1038/nature07761.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAmyloidosisAnimalsChlorocebus aethiopsCOS CellsHippocampusHumansLong-Term PotentiationMiceMice, Inbred C57BLNeuronal PlasticityNeuronsPeptide FragmentsPrionsProtein BindingProtein MultimerizationReceptors, Cell SurfaceSynapsesConceptsCellular prion protein PrPCPrion protein PrPCSoluble amyloid-β peptide (Aβ) oligomersAlzheimer's diseaseCellular prion proteinDisease pathologyPlasma membrane glycoproteinsCell surface receptorsHigh affinity cell surface receptorsAlzheimer's disease pathologySoluble Aβ oligomersLipid raftsInfectious prion diseasesUnexpected linkMechanistic basisMembrane glycoproteinsPrion proteinAmyloid-β peptide (Aβ) oligomersSynaptic plasticityPrion diseasesTherapeutic potentialDiseaseAβ oligomersCentral roleDeleterious effects