2021
TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use
Doulias P, Nakamura T, Scott H, McKercher S, Sultan A, Deal A, Albertolle M, Ischiropoulos H, Lipton S. TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use. Journal Of NeuroVirology 2021, 27: 367-378. PMID: 33876414, PMCID: PMC8477648, DOI: 10.1007/s13365-021-00970-4.Peer-Reviewed Original ResearchConceptsNeurocognitive disordersMeth usePathogenesis of HIVHuman postmortem brainAberrant protein S-nitrosylationCNS pathologyControl brainsSynaptic damageS-nitrosylationHIV-1Metabolic compromisePostmortem brainsMethamphetamine useNitric oxideDrug abuseRedox stressNitrosative stressBrainHIVProtein S-nitrosylationDisordersS-nitrosoproteomeSystematic inhibitionTCA cycle enzymesPathogenesisS-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
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
2013
Combating Oxidative/Nitrosative Stress with Electrophilic Counterattack Strategies
Satoh T, Akhtar M, Lipton S. Combating Oxidative/Nitrosative Stress with Electrophilic Counterattack Strategies. 2013, 277-307. DOI: 10.1007/978-94-007-5787-5_10.Peer-Reviewed Original ResearchPro-electrophilic drugsKeap1/Nrf2 pathwayTranscription-dependent pathwayCysteine thiol oxidationNitrosative stressOxidative stressStress-induced oxidationHeat shock proteinsRedox regulationSpecific cysteineProlonged oxidative stressNrf2 pathwayPhase 2 enzymesKeap1/Nrf2Redox stressThiol oxidationElectrophilic compoundsDefense systemHerb rosemaryPathwayNormal cellsCarnosic acidNeurodegenerative disordersCounterattack strategiesDeplete glutathione
2011
Redox 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
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 stress
2006
Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons
Yuan H, Gerencser A, Liot G, Lipton S, Ellisman M, Perkins G, Bossy-Wetzel E. Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons. Cell Death & Differentiation 2006, 14: 462-471. PMID: 17053808, DOI: 10.1038/sj.cdd.4402046.Peer-Reviewed Original ResearchConceptsMitochondrial fissionNitric oxideFoci formationCortical neuronsMitochondrial fission machineryBcl-2 familyNitrosative stressAntiapoptotic Bcl-xLNeuronal cell deathFission machineryMitofusin 1Puncta formationBioenergetic crisisBax accumulationMitochondrial inhibitorsNeuronal demiseBcl-xLCell deathMitochondrial dysfunctionMitochondriaNeurodegenerative disordersNO donorNeuronsScission siteFission