2024
“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 factorsEnzymeAlzheimerCascade
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
S-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
1999
Neuronal protection and destruction by NO
Lipton S. Neuronal protection and destruction by NO. Cell Death & Differentiation 1999, 6: 943-951. PMID: 10556970, DOI: 10.1038/sj.cdd.4400580.Peer-Reviewed Original ResearchConceptsS-nitrosylationCysteine residuesCaspase enzyme activityNeuronal apoptotic pathwayProtein functionCritical thiol groupsApoptotic pathwayMolecular switchReactive thiol groupsCritical thiolsN-methyl-D-aspartate receptor activityDisulfide bondsRedox stateThiol groupsDeath of neuronsSpeciesDifferent redox statesEnzyme activityDistinct chemical reactivityCaspasesPhysiological conditionsBiological activityActive siteResiduesReceptor activityRedox Sensitivity of NMDA Receptors
Lipton S. Redox Sensitivity of NMDA Receptors. Methods In Molecular Biology 1999, 128: 121-130. PMID: 10320978, DOI: 10.1385/1-59259-683-5:121.Peer-Reviewed Original ResearchConceptsCritical cysteine residuesCysteine residuesRedox modulationProtein cysteine residuesSite-directed mutagenesisEndogenous redox agentsRedox-related speciesFree sulfhydryl groupsProtein functionMolecular dataSulfhydryl groupsSufficient redox potentialCysteine sulfhydrylsRedox sensitivityCell typesNative NMDA receptorsDisulfide bondsNMDA receptor subunitsRedox modulatory siteRecombinant methodsReceptor consistReceptor subunitsOxygen speciesSingle thiol groupResidues
1998
NO-NMDA Receptor Interactions: A Neuromolecular Approach to Novel Therapeutics
Lipton S, Choi Y, Sucher N, Chen H. NO-NMDA Receptor Interactions: A Neuromolecular Approach to Novel Therapeutics. Ernst Schering Foundation Symposium Proceedings 1998, 95-108. DOI: 10.1007/978-3-662-03596-2_5.Peer-Reviewed Original ResearchRedox-related speciesFree sulfhydryl groupsSufficient redox potentialRedox modulationSulfhydryl groupsProtein cysteine residuesEndogenous redox agentsOrganic synthesisSingle sulfhydryl groupRedox potentialProtein functionRedox agentsCysteine residuesDistinctive chemistryNO groupCell typesDisulfide bondsGroup donorBiological systemsReceptor interactionDifferent biological effectsSpeciesOxygen speciesNovel therapeuticsEndogenous sources