2024
Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer’s and related dementias
Oh C, Nakamura T, Zhang X, Lipton S. Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer’s and related dementias. Neuron 2024, 112: 3823-3850. PMID: 39515322, PMCID: PMC11624102, DOI: 10.1016/j.neuron.2024.10.013.Peer-Reviewed Original ResearchProtein S-nitrosylationS-nitrosylationEndoplasmic reticulumRedox-mediated posttranslational modificationDiseases associated with protein aggregationProtein aggregationSynapse lossModulating protein activityNetwork of proteinsMultiple neurodegenerative disordersUbiquitin-proteasome systemS-nitrosylation reactionPosttranslational modificationsMitochondrial metabolismExcessive nitrosative stressEnzymatic machineryRedox regulationProtein activityProtein networkDysfunction pathwayMicroglial phagocytosisSingle proteinsBioenergetic compromiseReview recent findingsProteinUsing in vivo intact structure for system-wide quantitative analysis of changes in proteins
Son A, Kim H, Diedrich J, Bamberger C, McClatchy D, Lipton S, Yates J. Using in vivo intact structure for system-wide quantitative analysis of changes in proteins. Nature Communications 2024, 15: 9310. PMID: 39468068, PMCID: PMC11519357, DOI: 10.1038/s41467-024-53582-x.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProtein footprinting methodGlobal expression profilingIn vivo conformationStructural alterations of proteinsCo-expressed proteinsMass spectrometry-based methodsAlterations of proteinsProteostasis dysfunctionSpectrometry-based methodsProtein misfoldingConformation of proteinsStructural changesLysine residuesDynamic structural changesBiological functionsProteomics experimentsDimethyl labelingExpression profilesProtein conformationConformational changesProteinIntact proteinDesign of therapeutic interventionsMeasuring dynamic structural changesSingle‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets
Ghatak S, Diedrich J, Talantova M, Bhadra N, Scott H, Sharma M, Albertolle M, Schork N, Yates J, Lipton S. Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets. Advanced Science 2024, 11: e2400545. PMID: 38773714, PMCID: PMC11304297, DOI: 10.1002/advs.202400545.Peer-Reviewed Original ResearchAbundance of individual proteinsIsogenic wild-type controlsSingle-cell (scHuman AD brainsWild-type controlsSingle-cellAlzheimer's diseaseMulticellular organismsSingle-cell physiologyAD brainTherapeutic targetIndividual proteinsProteomic informationGenetic mutationsProteinProteomicsProtein expressionHiPSC-neuronsExcitatory neuronsElectrophysiological statusDisease statesPhysiologyElectrophysiological dataNeuronsNeuronal level“Dark” Pathways of Protein Transnitrosylation Injure Synapses in Alzheimer’s Disease: Mechanism and Potential Treatment
LIPTON S. “Dark” Pathways of Protein Transnitrosylation Injure Synapses in Alzheimer’s Disease: Mechanism and Potential Treatment. 2024, pl. DOI: 10.14869/toxpt.51.1.0_pl.Peer-Reviewed Original ResearchAlzheimer's diseaseDisruption of protein functionUbiquitin-protein hydrolaseS-nitrosylationS-nitrosylation reactionLoss of synapsesCorrelated to cognitive declineGuanosine triphosphataseMitochondrial fragmentationAD brainProtein functionAmyloid-betaAggregated proteinsProtein hydrolaseSynapse lossSynaptic lossBioenergetic compromiseSynaptic damageTransnitrosylation reactionsProteinUCH-L1Environmental factorsEnzymeAlzheimerCascadeEnzymatic and non-enzymatic transnitrosylation: “SCAN”ning the SNO-proteome
Nakamura T, Lipton S. Enzymatic and non-enzymatic transnitrosylation: “SCAN”ning the SNO-proteome. Molecular Cell 2024, 84: 191-193. PMID: 38242098, DOI: 10.1016/j.molcel.2023.12.018.Peer-Reviewed Original Research
2021
Protein S-Nitrosylation in Neuronal Development
Nakamura T, Zhang X, Oh C, Lipton S. Protein S-Nitrosylation in Neuronal Development. 2021, 91-105. DOI: 10.1201/9781003204091-10.Peer-Reviewed Original ResearchPost-translational modificationsProtein S-nitrosylationS-nitrosylationReactive nitrogen speciesNeuronal developmentNeuronal differentiationTranscription factor MEF2Protein-protein interactionsIon channel activityProtein traffickingEnzymatic functionCysteine thiolsProtein conformationCellular mechanismsChannel activityNormal brain developmentNitrogen speciesSynaptic functionNitric oxide actsPathological processesBiological actionsProteinNeuronal survivalBiological systemsNeurogenesisProtein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration
Nakamura T, Oh C, Zhang X, Lipton S. Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration. Free Radical Biology And Medicine 2021, 172: 562-577. PMID: 34224817, PMCID: PMC8579830, DOI: 10.1016/j.freeradbiomed.2021.07.002.Peer-Reviewed Original ResearchConceptsProtein misfoldingUbiquitin-proteasome systemCellular protein quality control machineryReactive oxygen speciesS-nitrosylationProtein quality control machineryQuality control machineryPost-translational modificationsNeurodegenerative diseasesProtein S-nitrosylationGenetic mutationsMost neurodegenerative diseasesMolecular chaperonesROS/RNSControl machineryLysosomal pathwayRare genetic mutationsMolecular mechanismsMolecular eventsMisfoldingMitochondrial dysfunctionTyrosine nitrationProteinOxygen speciesNeuronal demiseProtein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders
Nakamura T, Oh C, Zhang X, Tannenbaum S, Lipton S. Protein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders. Antioxidants & Redox Signaling 2021, 35: 531-550. PMID: 33957758, PMCID: PMC8388249, DOI: 10.1089/ars.2021.0081.Peer-Reviewed Original ResearchConceptsRelated reactive nitrogen speciesS-nitrosylationRedox-based posttranslational modificationProtein S-nitrosylationGlyceraldehyde-3-phosphate dehydrogenaseInhibitor of apoptosisThiol-containing proteinsNeurodegenerative diseasesSignaling networksPosttranslational modificationsReactive nitrogen speciesTransnitrosylation reactionsNuclear proteinsUnderstanding of agingCysteine thiolsTransnitrosylationBiochemical pathwaysChemical biologyMechanisms of diseaseProteinCaspase-3Nitrogen speciesUCH-L1Neurodegenerative disordersPhysiological concentrations
2017
Chapter 27 Aberrant Nitric Oxide Signaling Contributes to Protein Misfolding in Neurodegenerative Diseases via S-Nitrosylation and Tyrosine Nitration
Nakamura T, Lipton S. Chapter 27 Aberrant Nitric Oxide Signaling Contributes to Protein Misfolding in Neurodegenerative Diseases via S-Nitrosylation and Tyrosine Nitration. 2017, 373-384. DOI: 10.1016/b978-0-12-804273-1.00027-2.Peer-Reviewed Original ResearchReactive oxygen speciesS-nitrosylationProtein misfoldingProtein quality control machineryQuality control machineryAberrant S-nitrosylationUbiquitin-proteasome systemCysteine thiol groupsNeurodegenerative diseasesMolecular chaperonesMisfolded proteinsControl machineryMolecular mechanismsMitochondrial impairmentTyrosine nitrationPathological productionProteinMisfoldingSignaling contributesKey pathological featureOxygen speciesNeuronal demiseNitrogen speciesNitrosative stressGenetic risk factors
2007
Molecular mechanisms of nitrosative stress-mediated protein misfolding in neurodegenerative diseases
Nakamura T, Lipton S. Molecular mechanisms of nitrosative stress-mediated protein misfolding in neurodegenerative diseases. Cellular And Molecular Life Sciences 2007, 64: 1609-1620. PMID: 17453143, PMCID: PMC11136414, DOI: 10.1007/s00018-007-6525-0.Peer-Reviewed Original ResearchConceptsUbiquitin-proteasome systemNormal protein degradationProtein disulfide isomeraseMolecular chaperonesSpecific chaperonesGlucose-regulated protein 78Proper foldingProtein misfoldingAberrant proteinsProtein foldingUPS proteinsProtein degradationMolecular mechanismsShock proteinsConformational changesExcessive reactive oxygenCell deathNeuronal cell deathProteinChaperonesProtein 78Reactive oxygenMisfoldingNitrogen speciesNitrosative stressS-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding
Nakamura T, Lipton S. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding. Cell Death & Differentiation 2007, 14: 1305-1314. PMID: 17431424, DOI: 10.1038/sj.cdd.4402138.Peer-Reviewed Original ResearchConceptsS-nitrosylationProtein functionProtein misfoldingCell deathNeuronal cell deathProper protein foldingProtein disulfide isomeraseCysteine thiol groupsHeat shock proteinsExcessive NMDA receptor activityGlucose-regulated protein 78Neurodegenerative disordersProtein foldingExcitotoxic damageFree radical nitric oxideConformational changesMisfoldingForm of neurotoxicityRadical nitric oxideN-methyl-D-aspartate receptorsNitric oxideExcessive activityProteinProtein 78Chronic neurodegenerative disorders
1997
Suppression of neuronal apoptosis by S-nitrosylation of caspases
Tenneti L, D'Emilia D, Lipton S. Suppression of neuronal apoptosis by S-nitrosylation of caspases. Neuroscience Letters 1997, 236: 139-142. PMID: 9406756, DOI: 10.1016/s0304-3940(97)00780-5.Peer-Reviewed Original ResearchConceptsS-nitrosylationInterleukin-1beta-converting enzyme-like proteasesCritical cysteine residuesEnzyme-like proteasesApoptotic cell deathHuman embryonic kidneyTranscription factorsEnzyme familyCysteine residuesG proteinsEmbryonic kidneyCell deathCaspasesIon channelsPrimary cerebrocortical neuronsPhysiological activityEnzyme activityActive siteApoptosisNeuronal apoptosisCerebrocortical neuronsFamilyProteinProteaseEnzyme
1995
An astrocytic binding site for neuronal Thy-1 and its effect on neurite outgrowth.
Dreyer E, Leifer D, Heng J, McConnell J, Gorla M, Levin L, Barnstable C, Lipton S. An astrocytic binding site for neuronal Thy-1 and its effect on neurite outgrowth. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 11195-11199. PMID: 7479964, PMCID: PMC40598, DOI: 10.1073/pnas.92.24.11195.Peer-Reviewed Original ResearchConceptsNeurite outgrowthThy-1 functionsNeuronal Thy-1Thy-1Abundant glycoproteinMammalian neuronsNervous systemAnti-idiotype monoclonal antibodyCentral nervous system neuronsMonoclonal antibodiesBinding sitesCentral nervous systemAnti-idiotype antibodiesCertain monoclonal antibodiesBinding assaysCompetitive binding assaysProteinOutgrowthSystem neuronsDendritic developmentAntibodiesNeuronsSitesGlycoproteinCells
1993
Expression of endogenous NMDAR1 transcripts without receptor protein suggests post-transcriptional control in PC12 cells.
Sucher N, Brose N, Deitcher D, Awobuluyi M, Gasic G, Bading H, Cepko C, Greenberg M, Jahn R, Heinemann S, Lipton S. Expression of endogenous NMDAR1 transcripts without receptor protein suggests post-transcriptional control in PC12 cells. Journal Of Biological Chemistry 1993, 268: 22299-22304. PMID: 8226739, DOI: 10.1016/s0021-9258(18)41528-1.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAstrocytesBase SequenceCell DifferentiationCell LineCells, CulturedDimethylphenylpiperazinium IodideDNA PrimersGene ExpressionGene Expression Regulation, NeoplasticGenetic VariationHippocampusHumansKidneyMacromolecular SubstancesMembrane PotentialsMolecular Sequence DataMolecular WeightNerve Growth FactorsN-MethylaspartatePC12 CellsPolymerase Chain ReactionReceptors, N-Methyl-D-AspartateRNA, MessengerSynaptic MembranesTranscription, GeneticTransfectionConceptsNMDAR1 proteinPC12 cellsPost-transcriptional controlPost-transcriptional mechanismsNative PC12 cellsParticular cell typeUndifferentiated rat pheochromocytoma (PC12) cellsExpression of RNAPC12 cell lineTranslational regulationIsoform CRat pheochromocytoma cellsNorthern hybridizationExpression vectorReceptor proteinCell typesIon channelsProteinFunctional NMDACell linesPheochromocytoma cellsCytomegalovirus promoterModel systemRNAExpression
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply