2024
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
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
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 demiseS-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD
Pirie E, Oh C, Zhang X, Han X, Cieplak P, Scott H, Deal A, Ghatak S, Martinez F, Yeo G, Yates J, Nakamura T, Lipton S. S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2021368118. PMID: 33692125, PMCID: PMC7980404, DOI: 10.1073/pnas.2021368118.Peer-Reviewed Original ResearchConceptsProtein misfolding/aggregationCell spreadMisfolding/aggregationRNA-binding activityOligomerization/aggregationHuman-induced pluripotent stem cellsProtein TDP-43Pluripotent stem cellsALS/FTDTDP-43 aggregationTDP-43Cognate proteinProtein aggregationS-nitrosylationRare genetic mutationsCell-based modelFTD disordersAmyotrophic lateral sclerosisAbsence of mutationsTriggers aggregationStem cellsGenetic mutationsDisulfide linkagesNitrosative stressNeurodegenerative disorders
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