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
2012
Role of Cellular Prion Protein in the Amyloid-β Oligomer Pathophysiology of Alzheimer’s Disease
Kaufman A, Strittmatter S. Role of Cellular Prion Protein in the Amyloid-β Oligomer Pathophysiology of Alzheimer’s Disease. 2012, 35-48. DOI: 10.1007/978-1-4614-5305-5_3.Peer-Reviewed Original ResearchAlzheimer's diseaseMouse modelCellular prion proteinPrimary histopathological featureAD mouse modelAmyloid-beta plaquesTransgenic mouse modelLong-term potentiationHistopathological featuresPrion proteinNeuronal dysfunctionNeurofibrillary tanglesMemory deficitsMemory lossDiseaseExact mechanismCommon formEssential mediatorPathophysiologyToxic effectsCell deathPrPCHigh-affinity binding partnerSynaptotoxicityDysfunction
2010
Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin
Hu F, Padukkavidana T, Vægter CB, Brady OA, Zheng Y, Mackenzie IR, Feldman HH, Nykjaer A, Strittmatter SM. Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin. Neuron 2010, 68: 654-667. PMID: 21092856, PMCID: PMC2990962, DOI: 10.1016/j.neuron.2010.09.034.Peer-Reviewed Original ResearchConceptsFrontotemporal lobar degenerationSerum PGRN levelsFTLD-TDP casesFTLD-TDPMicroglial cellsPGRN levelsCortical neuronsGRN haploinsufficiencyProgranulin mutationsTDP-43Causative rolePGRNUbiquitin aggregatesNeuronsSortilinMiceCell surfaceDetermine levelsPathophysiologyInjuryProgranulinCNSCentral roleDegenerationBrain
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 monomersPrPCPathophysiologyNeurotoxicityPlaquesProgression