2024
Using 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 changes
2021
Protein 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 demise
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
2012
Redox control of protein misfolding and mitochondrial fragmentation via s-nitrosylation: Implications for synaptic damage in neurodegenerative diseases
Lipton⁎ S. Redox control of protein misfolding and mitochondrial fragmentation via s-nitrosylation: Implications for synaptic damage in neurodegenerative diseases. Free Radical Biology And Medicine 2012, 53: s29. DOI: 10.1016/j.freeradbiomed.2012.08.133.Peer-Reviewed Original Research
2011
Redox Regulation of Protein Misfolding, Synaptic Damage, and Neuronal Loss in Neurodegenerative Diseases
Nakamura T, Lipton S. Redox Regulation of Protein Misfolding, Synaptic Damage, and Neuronal Loss in Neurodegenerative Diseases. 2011, 65-99. DOI: 10.1002/9781118063903.ch2.Peer-Reviewed Original ResearchRedox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases
Nakamura T, Lipton S. Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases. Cell Death & Differentiation 2011, 18: 1478-1486. PMID: 21597461, PMCID: PMC3178424, DOI: 10.1038/cdd.2011.65.Peer-Reviewed Original ResearchConceptsS-nitrosylationProtein misfoldingCritical protein thiolsDynamin-related protein 1Protein disulfide isomeraseS-nitrosylation contributesNitrosative stressPosttranslational modificationsMitochondrial dynamicsNeuronal lossSynaptic damageDownstream pathwaysRedox modulationProtein thiolsNormal neuronal signalingMitochondrial dysfunctionN-methyl-D-aspartate (NMDA) receptor activationNeuronal signalingProtein 1Eventual neuronal lossNeuronal cell damageNeuronal cell injuryMisfoldingNeuronal NO synthaseNeurodegenerative diseases
2009
From Reactive Oxygen and Nitrogen Species to Therapy
McKercher S, Nakamura T, Lipton S. From Reactive Oxygen and Nitrogen Species to Therapy. 2009 DOI: 10.1002/9780470015902.a0021989.Peer-Reviewed Original ResearchReactive oxygen speciesProtein misfoldingS-nitrosylationE3 ubiquitin ligase ParkinUbiquitin ligase ParkinProtein disulfide isomeraseMisfolded protein aggregatesCritical cysteine thiolsS-nitrosylation reactionsExcessive reactive oxygen speciesNrf2 transcriptional pathwayProduction of ROSMisfolded proteinsProtein functionTranscriptional pathwaysCysteine thiolsProtein aggregatesMisfoldingReactive oxygenSpeciesPathological productionOxygen speciesGenetic mutationsNitrogen speciesNeurodegenerative diseases
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