2024
Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer’s and related dementias
Oh C, Nakamura T, Zhang X, Lipton S. Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer’s and related dementias. Neuron 2024 PMID: 39515322, DOI: 10.1016/j.neuron.2024.10.013.Peer-Reviewed Original ResearchProtein S-nitrosylationS-nitrosylationEndoplasmic reticulumRedox-mediated posttranslational modificationDiseases associated with protein aggregationProtein aggregationSynapse lossModulating protein activityNetwork of proteinsMultiple neurodegenerative disordersUbiquitin-proteasome systemS-nitrosylation reactionPosttranslational modificationsMitochondrial metabolismExcessive nitrosative stressEnzymatic machineryRedox regulationProtein activityProtein networkDysfunction pathwayMicroglial phagocytosisSingle proteinsBioenergetic compromiseReview recent findingsProtein
2022
S-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
2021
Protein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders
Nakamura T, Oh C, Zhang X, Tannenbaum S, Lipton S. Protein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders. Antioxidants & Redox Signaling 2021, 35: 531-550. PMID: 33957758, PMCID: PMC8388249, DOI: 10.1089/ars.2021.0081.Peer-Reviewed Original ResearchConceptsRelated reactive nitrogen speciesS-nitrosylationRedox-based posttranslational modificationProtein S-nitrosylationGlyceraldehyde-3-phosphate dehydrogenaseInhibitor of apoptosisThiol-containing proteinsNeurodegenerative diseasesSignaling networksPosttranslational modificationsReactive nitrogen speciesTransnitrosylation reactionsNuclear proteinsUnderstanding of agingCysteine thiolsTransnitrosylationBiochemical pathwaysChemical biologyMechanisms of diseaseProteinCaspase-3Nitrogen speciesUCH-L1Neurodegenerative disordersPhysiological concentrations
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 diseasesRole of the Mitochondrial Fission Protein Drp1 in Synaptic Damage and Neurodegeneration
Nakamura T, Cho D, Lipton S. Role of the Mitochondrial Fission Protein Drp1 in Synaptic Damage and Neurodegeneration. 2011, 215-234. DOI: 10.1007/978-94-007-1291-1_8.Peer-Reviewed Original ResearchMitochondrial fission protein Drp1Fission protein Drp1Mitochondrial fissionProtein Drp1Dynamin-related protein 1Abnormal mitochondrial morphologyMitochondrial fusionDrp1 activityPosttranslational modificationsMitochondrial morphologyMitochondrial structureCell deathDrp1Protein 1Recent insightsNeurodegenerative diseasesSynaptic damageNeuronal cell injuryNeurodegenerative conditionsFissionMitofusinsDynaminGTPasesFusionOPA1