2025
Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons
Pagano N, Perez G, Garcia-Milian R, Manuelidis L. Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons. PLOS ONE 2025, 20: e0323825. PMID: 40434970, PMCID: PMC12118874, DOI: 10.1371/journal.pone.0323825.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationCreutzfeldt-Jakob SyndromeHumansImmunity, InnateNeuronsRatsConceptsSeptal neuronsInnate immune responseDifferential transcriptionCreutzfeldt-Jakob disease agentCJ infectionImmune responseBind misfolded proteinsInnate immune genesIntestinal myeloid cellsRat septal neuronsArrests normal cellsDisease agentsInnate immune transcriptsCreutzfeldt-JakobModel of latent infectionAnti-viral responseCDNA libraryUnique transcriptsPeripheral human bloodLate-onset diseaseUninfected neuronsUpregulated interferonImmune genesMyeloid cellsTranscription
2023
Sporadic Creutzfeldt-Jakob Disease Initially Presenting With Posterior Reversible Encephalopathy Syndrome
Mikhaiel J, Parasram M, Manning T, Al-Dulaimi M, Barnes E, Falcone G, Hwang D, Prust M. Sporadic Creutzfeldt-Jakob Disease Initially Presenting With Posterior Reversible Encephalopathy Syndrome. The Neurologist 2023, 29: 14-16. PMID: 37582680, DOI: 10.1097/nrl.0000000000000519.Peer-Reviewed Original ResearchMeSH KeywordsActivities of Daily LivingAgedCreutzfeldt-Jakob SyndromeFemaleHumansMagnetic Resonance ImagingPosterior Leukoencephalopathy SyndromeConceptsSporadic Creutzfeldt-Jakob diseaseMagnetic resonance imagingReversible encephalopathy syndromeCreutzfeldt-Jakob diseaseEncephalopathy syndromeAntiseizure medicationsLumbar punctureDiagnosis of sCJDFluid-attenuated inversion recovery changesPosterior reversible encephalopathy syndromeRepeat magnetic resonance imagingCases of sCJDPeriodic dischargesMultiple antiseizure medicationsRepeat lumbar punctureStuporous mental stateInitial lumbar punctureInversion recovery hyperintensityNonconvulsive status epilepticusReal-time quaking-induced conversionFatal neurodegenerative conditionProgressive confusionRadiographic improvementNeurological declineStatus epilepticus
2018
Creutzfeldt–Jakob Disease
Narula R, Tinaz S. Creutzfeldt–Jakob Disease. New England Journal Of Medicine 2018, 378: e7. PMID: 29365304, DOI: 10.1056/nejmicm1710121.Peer-Reviewed Case Reports and Technical Notes
2016
CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection
Botsios S, Manuelidis L. CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection. Journal Of Cellular Biochemistry 2016, 117: 1947-1958. PMID: 26773845, DOI: 10.1002/jcb.25495.Peer-Reviewed Original ResearchConceptsTSE agentsTransmissible spongiform encephalopathiesAdaptive immune responsesDegenerative brain changesInfectious particlesHost prion proteinGT1 neuronal cellsForms of PrPLymphoreticular tissuesBrain changesImmune responseTSE strainsNeuronal cellsNeurodegenerative diseasesLatent virusInfectivity assaysSpongiform encephalopathiesNucleic acid genomeTitersEpidemic spreadViral structuresPrion proteinHost proteinsVirusHost components
2015
Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms
Botsios S, Tittman S, Manuelidis L. Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms. Virulence 2015, 6: 787-801. PMID: 26556670, PMCID: PMC4826107, DOI: 10.1080/21505594.2015.1098804.Peer-Reviewed Original ResearchConceptsInfectious titerInnate immune responseHuman CJDResistant virusesIatrogenic infectionGT1 cellsBrain changesImmune responseInfectious agentsTSE agentsScrapie agentCJDPrion protein amyloidSheep scrapieVirulent microbesInfectious particlesMin exposureIntrinsic resistanceTreatmentTitersPrP amyloidScrapieAmyloidCultured cellsDeep proteomic analysisProteomic analysis of host brain components that bind to infectious particles in Creutzfeldt‐Jakob disease
Kipkorir T, Colangelo CM, Manuelidis L. Proteomic analysis of host brain components that bind to infectious particles in Creutzfeldt‐Jakob disease. Proteomics 2015, 15: 2983-2998. PMID: 25930988, PMCID: PMC4601564, DOI: 10.1002/pmic.201500059.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCase-Control StudiesCreutzfeldt-Jakob SyndromeCyclin-Dependent Kinase Inhibitor p18CyclophilinsHSC70 Heat-Shock ProteinsHumansMicePrionsProteinsProteomicsConceptsCreutzfeldt-Jakob diseaseInfectious agentsTransmissible encephalopathiesNew therapeutic initiativesBrain particlesCausal infectious agentInfectious particlesHost prion proteinHost immune recognitionSynapsin-2Such therapyHost proteinsTherapeutic initiativesImmune recognitionStrain-specific patternsCommon pathwayCross-species transmissionHigh infectivityDiseaseViral pathwaysProteomic analysisHost targetsViral proteinsViral processingBrain components
2014
Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS
Kipkorir T, Tittman S, Botsios S, Manuelidis L. Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS. Journal Of Cellular Biochemistry 2014, 115: 2012-2021. PMID: 24933657, PMCID: PMC7166504, DOI: 10.1002/jcb.24873.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChromatography, LiquidCreutzfeldt-Jakob SyndromeHumansHuntingtin ProteinMiceNerve Tissue ProteinsPeptidesProteomicsPrPSc ProteinsTandem Mass SpectrometryVirulenceConceptsSporadic CJDMouse brainTransmissible encephalopathiesNormal human brain samplesHost prion proteinHuman brain samplesSCJD brainsPrion proteinAmyloid pathologyAPP processingNew therapiesUninfected controlsBrain homogenatesBrain samplesCellular findingsDetectable PrPNeurodegenerative diseasesSheep scrapieInfectious titerBrainProteinase KCJDLC-MS/MSViral motifsInfectious formLimbic Encephalitis Associated With Anti–Voltage-Gated Potassium Channel Complex Antibodies Mimicking Creutzfeldt-Jakob Disease
Yoo JY, Hirsch LJ. Limbic Encephalitis Associated With Anti–Voltage-Gated Potassium Channel Complex Antibodies Mimicking Creutzfeldt-Jakob Disease. JAMA Neurology 2014, 71: 79-82. PMID: 24247910, DOI: 10.1001/jamaneurol.2013.5179.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseFaciobrachial dystonic seizuresDystonic seizuresLimbic encephalitisPotassium channel complex antibodiesAbnormal basal gangliaCommon treatable conditionsMagnetic resonance imagingNonparaneoplastic formsProgressive confusionClinical featuresBasal gangliaTreatable conditionTreatable diseaseComplete resolutionSimilar presentationComplex antibodiesRapid onsetResonance imagingSyndromeEncephalitisReversible conditionDiseaseSeizuresImmunotherapy
2012
Continuous Production of Prions after Infectious Particles Are Eliminated: Implications for Alzheimer’s Disease
Miyazawa K, Kipkorir T, Tittman S, Manuelidis L. Continuous Production of Prions after Infectious Particles Are Eliminated: Implications for Alzheimer’s Disease. PLOS ONE 2012, 7: e35471. PMID: 22509412, PMCID: PMC3324552, DOI: 10.1371/journal.pone.0035471.Peer-Reviewed Original Research
2011
High CJD infectivity remains after prion protein is destroyed
Miyazawa K, Emmerling K, Manuelidis L. High CJD infectivity remains after prion protein is destroyed. Journal Of Cellular Biochemistry 2011, 112: 3630-3637. PMID: 21793041, PMCID: PMC3202053, DOI: 10.1002/jcb.23286.Peer-Reviewed Original ResearchConceptsTransmissible spongiform encephalopathy agentsSpongiform encephalopathy agentInfectious particlesHost prion proteinPK digestionTotal PrPCJD infectivityInfectious homogenatesPrion proteinBrain resultsHigh titersTitersCell infectivityCell-based assaysCell culture assaysInfectivityProteinase K treatmentInfectious formPrPBrainCulture assaysAssaysProteinSensitive formK treatmentReplication and spread of CJD, kuru and scrapie agents in vivo and in cell culture
Miyazawa K, Emmerling K, Manuelidis L. Replication and spread of CJD, kuru and scrapie agents in vivo and in cell culture. Virulence 2011, 2: 188-199. PMID: 21527829, PMCID: PMC3149681, DOI: 10.4161/viru.2.3.15880.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Culture TechniquesCell LineCreutzfeldt-Jakob SyndromeDisease Models, AnimalHumansImmunity, InnateKuruMicePrionsRodent DiseasesScrapieSheepTime FactorsConceptsGT1 cellsSporadic CJDTSE agentsScrapie agentAgent-specific patternsTransmissible spongiform encephalopathy agentsComplex innate immune responseSpongiform encephalopathy agentInnate immune responseHost prion proteinK scrapie agentHuman CJDCJD agentNeuropathological sequelaeBrain titersImmune responseHuman kuruClearance mechanismsCJDInhibitory effectEnvironmental agentsCell-based assaysKuruInfectious formDistinct incubation times
2010
Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD
Manuelidis L. Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD. Journal Of NeuroVirology 2010, 17: 131-145. PMID: 21165784, DOI: 10.1007/s13365-010-0007-0.Peer-Reviewed Original ResearchMeSH KeywordsAcinetobacterAmino Acid SequenceAnimalsBase SequenceBrainConserved SequenceCreutzfeldt-Jakob SyndromeCricetinaeDeoxyribonucleasesDNA HelicasesDNA, CircularDNA, MitochondrialDNA-Directed DNA PolymeraseElectrophoresis, Agar GelGenome, BacterialHumansMiceMolecular Sequence DataNeuroblastomaNeurodegenerative DiseasesPlasmidsPolymerase Chain ReactionPrionsScrapieTumor Cells, Cultured
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 monomersPrPCPathophysiologyNeurotoxicityPlaquesProgressionThe kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents
Manuelidis L, Chakrabarty T, Miyazawa K, Nduom NA, Emmerling K. The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 13529-13534. PMID: 19633190, PMCID: PMC2715327, DOI: 10.1073/pnas.0905825106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCattleCells, CulturedCreutzfeldt-Jakob SyndromeGeographyHumansKuruMiceNeuronsPrionsScrapieSheepTime FactorsTissue Culture TechniquesConceptsSporadic Creutzfeldt-Jakob diseaseCreutzfeldt-Jakob diseaseBovine spongiform encephalopathyBSE agentHuman sporadic Creutzfeldt-Jakob diseaseInfectious agentsEpidemic bovine spongiform encephalopathyTSE agentsScrapie agentTransmissible spongiform encephalopathy agentsSpongiform encephalopathy agentKuru agentLymphoreticular involvementBrain neuropathologySporadic CJDGT1 cellsNormal miceInfected humansNeurodegenerative diseasesDiseaseViral receptorsInfectious neurodegenerative diseasesSheep scrapieSpongiform encephalopathiesHigh levels
2008
Strain‐specific viral properties of variant Creutzfeldt–Jakob disease (vCJD) are encoded by the agent and not by host prion protein
Manuelidis L, Liu Y, Mullins B. Strain‐specific viral properties of variant Creutzfeldt–Jakob disease (vCJD) are encoded by the agent and not by host prion protein. Journal Of Cellular Biochemistry 2008, 106: 220-231. PMID: 19097123, PMCID: PMC2762821, DOI: 10.1002/jcb.21988.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCattleCreutzfeldt-Jakob SyndromeCricetinaeHumansPrion DiseasesPrionsSerial PassageSheepSpecies SpecificityConceptsVariant Creutzfeldt-Jakob diseaseBovine spongiform encephalopathyTransmissible spongiform encephalopathiesVCJD agentTSE strainsInfectious agentsNeuronal culturesEpidemic bovine spongiform encephalopathyMost viral infectionsCreutzfeldt-Jakob diseaseSpongiform encephalopathiesHost prion proteinHost PrP.Human CJDRegional neuropathologyVCJD brainPrion proteinSheep scrapie agentVariant CJDStrain-specific characteristicsBSE strainBrain homogenatesViral infectionPrimate brainScrapie agent
2004
New molecular markers of early and progressive CJD brain infection
Lu ZY, Baker CA, Manuelidis L. New molecular markers of early and progressive CJD brain infection. Journal Of Cellular Biochemistry 2004, 93: 644-652. PMID: 15660413, DOI: 10.1002/jcb.20220.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseBrain infectionTransmissible spongiform encephalopathiesHuman Creutzfeldt-Jakob diseaseAccessible peripheral tissuesL-selectin mRNASerum amyloid A3Progressive diseaseInflammatory pathwaysMIP-1alphaMIP-1betaIntracerebral inoculationPeripheral tissuesEarly diagnosisTSE infectionInfectious componentNormal brainTSE strainsInfectious agentsMyeloid cellsSimilar sequential changesImmune systemMouse brainTSE agentsNew molecular markersEarly induction of interferon-responsive mRNAs in Creutzfeldt-Jakob disease
Baker CA, Lu ZY, Manuelidis L. Early induction of interferon-responsive mRNAs in Creutzfeldt-Jakob disease. Journal Of NeuroVirology 2004, 10: 29-40. PMID: 14982726, PMCID: PMC4624297, DOI: 10.1080/13550280490261761.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseCJD agentCJD brainsInterferon-sensitive genesImmune responseForeign infectious agentsHost immune responseAbnormal prion proteinHost defense mechanismsMicroglial responseInflammatory pathwaysClinical signsPure microgliaViral infectionInfectious agentsWhole brainImmune recognitionPersistent virusesInterferon responsePreclinical diagnosisInfectionEarly inductionBrainMicrogliaGene expression profiles
2003
Unique inflammatory RNA profiles of microglia in Creutzfeldt–Jakob disease
Baker CA, Manuelidis L. Unique inflammatory RNA profiles of microglia in Creutzfeldt–Jakob disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 675-679. PMID: 12525699, PMCID: PMC141055, DOI: 10.1073/pnas.0237313100.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseMyeloid cellsUninfected microgliaInflammatory pathwaysMicroglial cellsIFN-gammaInflammatory stimuliMicrogliaInflammatory genesProtein pathologyInfectious agentsPreclinical diagnosisNeurodegenerative diseasesTransmissible spongiformDiseaseBrainPrP amyloidRNA profilesExpression profilesCellsCDNA arraysPrevious studiesInfectionDiagnosisPathology
2002
Microglia from Creutzfeldt-Jakob Disease-Infected Brains Are Infectious and Show Specific mRNA Activation Profiles
Baker CA, Martin D, Manuelidis L. Microglia from Creutzfeldt-Jakob Disease-Infected Brains Are Infectious and Show Specific mRNA Activation Profiles. Journal Of Virology 2002, 76: 10905-10913. PMID: 12368333, PMCID: PMC136595, DOI: 10.1128/jvi.76.21.10905-10913.2002.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid beta-PeptidesAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticBrainCD40 AntigensChemokine CXCL10Chemokines, CXCCreutzfeldt-Jakob SyndromeGene ExpressionGene Expression ProfilingInterleukin-1Leukocyte Common AntigensLipopolysaccharidesMiceMicrogliaReceptor, Macrophage Colony-Stimulating FactorReceptors, CCR5RNA, MessengerTumor Necrosis Factor-alphaConceptsCreutzfeldt-Jakob diseaseCJD agentInfectious agentsCJD-infected miceB lymphocyte chemoattractantCytokine interleukin-1betaResult of infectionPathological prion proteinBrain cell typesMicroglial studiesMicroglial changesMicroglial markersReverse transcription-PCRAntigen presentationInterleukin-1betaBrain homogenatesMicrogliaPrP levelsBacterial lipopolysaccharideCellular activationPathological PrPActivated cellsBovine spongiformSpongiform encephalopathiesMolecular pathways
2001
Blood borne transit of CJD from brain to gut at early stages of infection
Radebold K, Chernyak M, Martin D, Manuelidis L. Blood borne transit of CJD from brain to gut at early stages of infection. BMC Infectious Diseases 2001, 1: 20. PMID: 11716790, PMCID: PMC59894, DOI: 10.1186/1471-2334-1-20.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCreutzfeldt-Jakob SyndromeDigestive SystemDisease Models, AnimalMicePrPSc ProteinsConceptsCreutzfeldt-Jakob diseaseIC inoculationAbnormal PrPCJD agentTransmissible spongiform encephalopathiesLymphoreticular tissuesEnteric infectionsIp inoculationPrP accumulationSpinal cordPeripheral tissuesGastrointestinal tractInfectious inoculumLymphatic drainageInfectious agentsVascular routeCell infectivityInfectionTerminal stageDiseaseSpongiform encephalopathiesDifferent organsBrainDaysProgressive appearance
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