2019
Hsp110 mitigates α-synuclein pathology in vivo
Taguchi YV, Gorenberg EL, Nagy M, Thrasher D, Fenton WA, Volpicelli-Daley L, Horwich AL, Chandra SS. Hsp110 mitigates α-synuclein pathology in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24310-24316. PMID: 31685606, PMCID: PMC6883785, DOI: 10.1073/pnas.1903268116.Peer-Reviewed Original ResearchConceptsΑ-synuclein pathologyOverexpression of Hsp110Α-synuclein aggregationPresynaptic protein α-synucleinΑ-synuclein seedsΑ-synuclein oligomersLewy bodiesMouse modelParkinson's diseaseCell culture modelSynaptic proteomeΑ-synucleinProtein α-synucleinPathologyCulture modelDiseaseMammalian cell culture modelsProtein changesOverexpressionVivoHsp110Molecular facilitatorsMiceUnbiased analysisBrain
2016
Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice
Hadzipasic M, Ni W, Nagy M, Steenrod N, McGinley MJ, Kaushal A, Thomas E, McCormick DA, Horwich AL. Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e7600-e7609. PMID: 27821773, PMCID: PMC5127366, DOI: 10.1073/pnas.1616832113.Peer-Reviewed Original ResearchConceptsALS miceAmyotrophic lateral sclerosisAcute spinal cord slicesSingle-unit extracellular recordingsWhole-cell patch-clamp recordingsLoss of neuronsMotor neuron lossMotor neuron firingSpinal cord slicesPatch-clamp recordingsHigh-frequency firingStep variabilityLethal neurodegenerative diseaseNeuron lossCord slicesSpinal cordLeg flexorsLateral sclerosisGait variabilityVivo effectsClamp recordingsExtracellular recordingsEMG patternsMutant miceNeuron firing
2014
Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS
Hadzipasic M, Tahvildari B, Nagy M, Bian M, Horwich AL, McCormick DA. Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16883-16888. PMID: 25385594, PMCID: PMC4250117, DOI: 10.1073/pnas.1419497111.Peer-Reviewed Original ResearchConceptsMN cell bodiesMotor neuronsMo of ageCell bodiesSpinal cordSpinal cord tissue slicesWhole-cell patch-clamp recordingsCell patch-clamp recordingsAdult mouse spinal cordIntrinsic electrophysiologic propertiesTwitch muscleSpinal motor neuronsLower extremity musclesTransgenic mouse modelMouse motor neuronsPatch-clamp recordingsAmyotrophic lateral sclerosisMouse spinal cordSlow-twitch muscleSteady-state firing ratePhysiological subtypesRetrograde tracingAcute slicesExtremity musclesPathophysiologic eventsProduction of RNA for Transcriptomic Analysis from Mouse Spinal Cord Motor Neuron Cell Bodies by Laser Capture Microdissection
Bandyopadhyay U, Fenton WA, Horwich AL, Nagy M. Production of RNA for Transcriptomic Analysis from Mouse Spinal Cord Motor Neuron Cell Bodies by Laser Capture Microdissection. Journal Of Visualized Experiments 2014, 51168. PMID: 24457537, PMCID: PMC4089401, DOI: 10.3791/51168.Peer-Reviewed Original ResearchConceptsLaser capture microdissectionMotor neuronsSpinal cordMotor neuron cell bodiesCapture microdissectionMouse spinal cordNeuron cell bodiesTotal cell populationCell typesPharmacologic treatmentStained neuronsCell bodiesNeurodegenerative diseasesNeuronsExogenous RNasesQRT-PCRSame cell typeCell populationsCordRNA damageDiseaseTotal RNASuch preparationsMicrodissectionTranscriptional differences
2013
Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm
Song Y, Nagy M, Ni W, Tyagi NK, Fenton WA, López-Giráldez F, Overton JD, Horwich AL, Brady ST. Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 5428-5433. PMID: 23509252, PMCID: PMC3619309, DOI: 10.1073/pnas.1303279110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonal TransportBacterial ProteinsDecapodiformesGene Expression ProfilingHSP110 Heat-Shock ProteinsHumansLuminescent ProteinsMAP Kinase Kinase Kinase 5MiceMice, TransgenicMutation, MissenseP38 Mitogen-Activated Protein KinasesPhosphorylationProtein FoldingProteomicsRecombinant Fusion ProteinsSpinal CordSuperoxide DismutaseSuperoxide Dismutase-1Transport VesiclesConceptsMutant SOD1 proteinTransport defectSOD1 proteinApoptosis signal-regulating kinase 1 inhibitorsPhosphorylation of kinesinNucleotide exchange factorsMolecular chaperone Hsc70Different oligomeric statesYellow fluorescent proteinTransgenic miceProtein disaggregationChaperone Hsc70Exchange factorMAPK cascadePhosphorylation of p38Oligomeric stateDiminished phosphorylationKinase 1 inhibitorFusion proteinFluorescent proteinP38 inhibitorP38 MAPKPhosphorylationHsp110Cu/ZnRNA-Seq Profiling of Spinal Cord Motor Neurons from a Presymptomatic SOD1 ALS Mouse
Bandyopadhyay U, Cotney J, Nagy M, Oh S, Leng J, Mahajan M, Mane S, Fenton WA, Noonan JP, Horwich AL. RNA-Seq Profiling of Spinal Cord Motor Neurons from a Presymptomatic SOD1 ALS Mouse. PLOS ONE 2013, 8: e53575. PMID: 23301088, PMCID: PMC3536741, DOI: 10.1371/journal.pone.0053575.Peer-Reviewed Original ResearchConceptsRNA metabolismMutant proteinsMotor neuron cell bodiesPost-translational effectsRNA-seq profilingMotor neuronsNeuron cell bodiesWhole transcriptome profilingMonths of ageAltered expression levelsMutant human SOD1Transcriptome profilingLower motor neuron cell bodiesCell bodiesTransgenic strainsSpinal cord motor neuronsSymptoms of ALSMutant SOD1 miceSOD1-ALS miceAge-matched animalsHuman SOD1Amyotrophic lateral sclerosisProtein TDP43Expression levelsForms of ALS