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
2022
Mechanistic insight into female predominance in Alzheimer’s disease based on aberrant protein S-nitrosylation of C3
Yang H, Oh C, Amal H, Wishnok J, Lewis S, Schahrer E, Trudler D, Nakamura T, Tannenbaum S, Lipton S. Mechanistic insight into female predominance in Alzheimer’s disease based on aberrant protein S-nitrosylation of C3. Science Advances 2022, 8: eade0764. PMID: 36516243, PMCID: PMC9750152, DOI: 10.1126/sciadv.ade0764.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseBrainFemaleHumansMaleProtein Processing, Post-TranslationalProteinsSynapsesConceptsAlzheimer's diseaseAD brainPostmortem Alzheimer's diseaseComplement component 3Sex-dependent mannerConsequent cognitive declineSynaptic phagocytosisΒ-estradiol levelsFemale predominanceAberrant protein S-nitrosylationSynaptic damageAD pathogenesisSNO proteinsCognitive declineProtein SDiseaseRobust alterationsBrainComponent 3Protein S-nitrosylationHuman brainS-nitrosylationS-nitrosoproteomePatientsPathogenesisHidden networks of aberrant protein transnitrosylation contribute to synapse loss in Alzheimer's disease
Lipton S. Hidden networks of aberrant protein transnitrosylation contribute to synapse loss in Alzheimer's disease. Free Radical Biology And Medicine 2022, 193: 171-176. PMID: 36243209, PMCID: PMC9875813, DOI: 10.1016/j.freeradbiomed.2022.10.272.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseParkinson's diseaseNitric oxideSoluble guanylate cyclaseFormation of peroxynitriteSynapse lossNeurocognitive disordersNeurological disordersDiseaseGuanylate cyclaseNeurodevelopmental disordersDisordersProtein S-nitrosylationSuperoxide anionTyrosine nitrationS-nitrosylationHIVS-nitrosationPathogenesisDementiaS-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders
Kim K, Cho E, Eom J, Oh S, Nakamura T, Oh C, Lipton S, Kim Y. S-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders. Cell Death & Differentiation 2022, 29: 2137-2150. PMID: 35462559, PMCID: PMC9613756, DOI: 10.1038/s41418-022-01004-0.Peer-Reviewed Original ResearchConceptsS-nitrosylationProtein aggregatesAutophagic fluxProtein S-nitrosylationBlocks autophagic fluxCathepsin BCaspase-dependent neuronal apoptosisPosttranslational modificationsProtease cathepsin BEnzymatic functionLysosomal protease cathepsin BCTSB activityChemical inhibitorsCA-074MeHuman AD brainsEnzymatic activityCysteineNeurodegenerative disordersPostmortem human AD brainTransgenic miceNeuronal apoptosisCTSBAccumulationAD pathogenesisAlzheimer's disease
2006
Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers
Satoh T, Okamoto S, Cui J, Watanabe Y, Furuta K, Suzuki M, Tohyama K, Lipton S. Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 768-773. PMID: 16407140, PMCID: PMC1334635, DOI: 10.1073/pnas.0505723102.Peer-Reviewed Original ResearchConceptsNeurite outgrowth-promoting prostaglandinsHemeoxygenase-1Cerebral ischemia/reperfusion injuryKeap1/Nrf2/HOIschemia/reperfusion injuryGlutamate-related excitotoxicityKeap1/Nrf2 pathwayNrf2/HOHO-1 expressionCultured neuronal cellsInactivation of Nrf2Phase II enzymesThiol-dependent mannerTranscription factor Nrf2HO-1 promoterNeuroprotective actionReperfusion injuryNeuroprotective compoundsNrf2 pathwayTherapeutic approachesNrf2 translocationAntioxidant responsive elementNeurodegenerative disordersNeuronal cellsFactor Nrf2
2005
Nitrosative and oxidative stress links dysfunctional ubiquitination to Parkinson's disease
Gu Z, Nakamura T, Yao D, Shi Z, Lipton S. Nitrosative and oxidative stress links dysfunctional ubiquitination to Parkinson's disease. Cell Death & Differentiation 2005, 12: 1202-1204. PMID: 16094397, DOI: 10.1038/sj.cdd.4401705.Peer-Reviewed Original Research