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
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
2013
Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein
Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, Takahashi H, Kerrisk ME, Vortmeyer A, Wisniewski T, Koleske AJ, Gunther EC, Nygaard HB, Strittmatter SM. Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein. Neuron 2013, 79: 887-902. PMID: 24012003, PMCID: PMC3768018, DOI: 10.1016/j.neuron.2013.06.036.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCalciumCells, CulturedElongation Factor 2 KinaseHEK293 CellsHumansMiceNeuronsOocytesPhosphorylationPost-Synaptic DensityProto-Oncogene Proteins c-fynPrPC ProteinsReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateSignal TransductionXenopusConceptsDisease pathophysiologyHuman AD brain extractsCellular prion proteinMetabotropic glutamate receptor 5Postsynaptic densityDendritic spine lossAD brain extractsMetabotropic glutamate receptorsGlutamate receptor 5Alzheimer's disease pathophysiologyExtracellular AβOsMGluR5 antagonismPrion proteinSpine lossSynapse densityGlutamate receptorsIntracellular calciumMGluR5Receptor 5Neuronal functionAβOsBrain extractsAβ oligomersFyn kinasePSD proteins