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
2016
Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity
Smith LM, Strittmatter SM. Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity. Cold Spring Harbor Perspectives In Medicine 2016, 7: a024075. PMID: 27940601, PMCID: PMC5411685, DOI: 10.1101/cshperspect.a024075.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAβ oligomersSoluble Aβ oligomersFibrillary amyloidNeuronal impairmentSynaptic dysfunctionAD pathogenesisSynaptic toxicityAmyloid-β OligomersCellular prion proteinNeuronal cascadesFurther studiesCell surface proteinsDiseaseAβPrion proteinOligomer toxicityToxicityDysfunctionMolecular basisPathogenesisDementiaProteinPlaquesImpairmentOligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease*
Haas LT, Strittmatter SM. Oligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease*. Journal Of Biological Chemistry 2016, 291: 17112-17121. PMID: 27325698, PMCID: PMC5016115, DOI: 10.1074/jbc.m116.720664.Peer-Reviewed Original ResearchConceptsProtein tyrosine kinase 2Calmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IICellular prion proteinProtein kinase IIBrain slicesSignaling cascadesAlzheimer's diseaseKinase IIPhysiological signalingKinase 2Mutant transgeneMetabotropic glutamate receptor 5Loss of synapsesPrion proteinGlutamate receptor 5Receptor complexWild-type slicesProtein mediatorsAmyloid-β OligomersGlutamate activationChronic expressionDementia symptomsReceptor 5Acute exposure
2014
Therapeutic Molecules and Endogenous Ligands Regulate the Interaction between Brain Cellular Prion Protein (PrPC) and Metabotropic Glutamate Receptor 5 (mGluR5)*
Haas LT, Kostylev MA, Strittmatter SM. Therapeutic Molecules and Endogenous Ligands Regulate the Interaction between Brain Cellular Prion Protein (PrPC) and Metabotropic Glutamate Receptor 5 (mGluR5)*. Journal Of Biological Chemistry 2014, 289: 28460-28477. PMID: 25148681, PMCID: PMC4192497, DOI: 10.1074/jbc.m114.584342.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsAntibodiesBinding SitesBiological AssayBrain ChemistryCell MembraneDisease Models, AnimalGene Expression RegulationHEK293 CellsHumansLigandsMiceMice, TransgenicPeptide MappingProtein BindingProtein Structure, TertiaryPrPC ProteinsReceptor, Metabotropic Glutamate 5Recombinant ProteinsSignal TransductionSmall Molecule LibrariesConceptsMetabotropic glutamate receptor 5Glutamate receptor 5Receptor 5Endogenous ligandMouse brainAD transgenic model miceCellular prion proteinAmino acids 91Transgenic model miceSoluble amyloid β (Aβ) oligomersAlzheimer's disease pathophysiologySilent allosteric modulatorsAgonists/antagonistsExtracellular AβOsMGluR5 activitySynthetic AβOsPrion proteinAmyloid-β OligomersModel miceCell membrane preparationsMGluR5Neurotoxic signalsBrain homogenatesAlzheimer's diseaseDisease pathophysiology
2013
Amyloid-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