2025
S-Nitrosylation of CRTC1 in Alzheimer’s disease impairs CREB-dependent gene expression induced by neuronal activity
Zhang X, Vlkolinsky R, Wu C, Dolatabadi N, Scott H, Prikhodko O, Zhang A, Blanco M, Lang N, Piña-Crespo J, Nakamura T, Roberto M, Lipton S. S-Nitrosylation of CRTC1 in Alzheimer’s disease impairs CREB-dependent gene expression induced by neuronal activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2418179122. PMID: 40014571, PMCID: PMC11892585, DOI: 10.1073/pnas.2418179122.Peer-Reviewed Original ResearchConceptsActivity-dependent gene expressionGene expressionAlzheimer's diseaseCREB-dependent gene expressionS-nitrosylationNitric oxide (NO)-related speciesTargets of S-nitrosylationNeuronal activity-dependent gene expressionPathogenesis of ADDecreased neurite lengthIncreased neuronal cell deathNeuronal cell deathSynaptic plasticityTranscriptional pathwaysCell deathCRISPR/Cas9 techniqueTranscription coactivator 1AD modelLong-term memory formationIncreased S-nitrosylationLong-term potentiationTherapeutic targetExpressionNeurite lengthCerebrocortical neurons
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
2023
Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression
Tse W, Pochwat B, Szewczyk B, Misztak P, Bobula B, Tokarski K, Worch R, Czarnota-Bojarska M, Lipton S, Zaręba-Kozioł M, Bijata M, Wlodarczyk J. Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression. Neuropharmacology 2023, 241: 109729. PMID: 37797736, DOI: 10.1016/j.neuropharm.2023.109729.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexLong-term potentiationChronic restraint stress mouse modelSynaptic plasticityN-methyl-D-aspartate receptor antagonistRestraint stress mouse modelMale C57BL/6J miceAntidepressant-like activityTail suspension testStress mouse modelFunctional synaptic plasticityMajor depressive disorderAntidepressant potentialPharmacological treatmentPsychotomimetic effectsReceptor antagonistC57BL/6J miceDepressive behaviorSucrose preferenceDepressive disorderNitroSynapsinMouse modelSuspension testBehavioral disturbancesCerebrocortical neuronsPivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis
Okuda K, Nakahara K, Ito A, Iijima Y, Nomura R, Kumar A, Fujikawa K, Adachi K, Shimada Y, Fujio S, Yamamoto R, Takasugi N, Onuma K, Osaki M, Okada F, Ukegawa T, Takeuchi Y, Yasui N, Yamashita A, Marusawa H, Matsushita Y, Katagiri T, Shibata T, Uchida K, Niu S, Lang N, Nakamura T, Zhang K, Lipton S, Uehara T. Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis. Nature Communications 2023, 14: 621. PMID: 36739439, PMCID: PMC9899281, DOI: 10.1038/s41467-023-36232-6.Peer-Reviewed Original ResearchConceptsS-nitrosylationDNA methyltransferasesEnzymatic activityGene expressionDe novo DNA methylationNovo DNA methylationAberrant S-nitrosylationProtein S-nitrosylationDNA methyltransferase 3BDNMT enzymatic activityStructure-based virtual screeningEpigenetic regulationDNA methylationCysteine residuesMethyltransferase 3BVivo cancer modelsS-adenosylAberrant upregulationNeoplastic cell proliferationHuman colonic adenomasMethylationCyclin D2Cell proliferationTumor formationDNMT3B
2022
Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging
Cabral‐Miranda F, Tamburini G, Martinez G, Ardiles A, Medinas D, Gerakis Y, Hung M, Vidal R, Fuentealba M, Miedema T, Duran‐Aniotz C, Diaz J, Ibaceta‐Gonzalez C, Sabusap C, Bermedo‐Garcia F, Mujica P, Adamson S, Vitangcol K, Huerta H, Zhang X, Nakamura T, Sardi S, Lipton S, Kennedy B, Henriquez J, Cárdenas J, Plate L, Palacios A, Hetz C. Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging. The EMBO Journal 2022, 41: embj2022111952. PMID: 36314651, PMCID: PMC9670206, DOI: 10.15252/embj.2022111952.Peer-Reviewed Original ResearchConceptsUnfolded protein responseER stress sensor IRE1Stress sensor IRE1IRE1/XBP1 signalingTranscription factor XBP1Mammalian brain agingNeurodegenerative diseasesProteostasis networkEndoplasmic reticulum stressProteomic profilingProtein responseCell senescenceGenetic disruptionBrain agingXBP1 expressionReticulum stressMammalian brainMajor risk factorActive formHealthy brain agingSynaptic functionXBP1Age-related cognitive declinePathwayHippocampal tissueTowards development of disease-modifying therapy for Alzheimer's disease using redox chemical biology pathways
Lipton S. Towards development of disease-modifying therapy for Alzheimer's disease using redox chemical biology pathways. Current Opinion In Pharmacology 2022, 66: 102267. PMID: 35870288, PMCID: PMC9509422, DOI: 10.1016/j.coph.2022.102267.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseDisease-modifying therapiesPotential therapeutic efficacySevere side effectsPotential therapeutic targetCerebral organoid modelTranscription factor Nrf2Absence of diseaseNMDA typeGlutamate receptorsDisease processSide effectsTherapeutic targetTransgenic miceTherapeutic efficacyNeurodegenerative disordersNormal tissuesDiseaseFactor Nrf2Organoid modelsProtein S-nitrosylationS-nitrosylationProtein Keap1TherapyNrf2S-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 diseaseS-Nitrosylation of p62 Inhibits Autophagic Flux to Promote α-Synuclein Secretion and Spread in Parkinson's Disease and Lewy Body Dementia
Oh C, Dolatabadi N, Cieplak P, Diaz-Meco M, Moscat J, Nolan J, Nakamura T, Lipton S. S-Nitrosylation of p62 Inhibits Autophagic Flux to Promote α-Synuclein Secretion and Spread in Parkinson's Disease and Lewy Body Dementia. Journal Of Neuroscience 2022, 42: 3011-3024. PMID: 35169022, PMCID: PMC8985870, DOI: 10.1523/jneurosci.1508-21.2022.Peer-Reviewed Original ResearchConceptsLewy body dementiaParkinson's diseaseAutophagic fluxInhibits autophagic fluxΑ-synucleinPluripotent stem cell-derived neuronsStem cell-derived neuronsΑ-synuclein secretionS-nitrosylationCell-derived neuronsHuman postmortem brainProtein S-nitrosylationΑ-synuclein aggregationPostmortem brainsConsequent secretionPathologic pathwaysNervous systemAdaptor protein p62Autophagic inhibitionDysfunctional autophagyNeurodegenerative disordersDiseaseIndividual neuronsDementiaSecretion
2021
Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation
Xian H, Liu Y, Rundberg Nilsson A, Gatchalian R, Crother T, Tourtellotte W, Zhang Y, Aleman-Muench G, Lewis G, Chen W, Kang S, Luevanos M, Trudler D, Lipton S, Soroosh P, Teijaro J, de la Torre J, Arditi M, Karin M, Sanchez-Lopez E. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity 2021, 54: 1463-1477.e11. PMID: 34115964, PMCID: PMC8189765, DOI: 10.1016/j.immuni.2021.05.004.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeInflammasome activationSARS-CoV-2-induced acute respiratory distress syndromeMyeloid-specific ablationSevere COVID-19Anti-diabetic medicationsAnti-inflammatory effectsRespiratory distress syndromeIL-6 secretionNLRP3 inflammasome activationHigh mortality rateCOVID-19 lungsInhibition of ATPDistress syndromePulmonary inflammationIL-6Inflammatory conditionsMetformin inhibitionMetformin inhibitsARDS severityNF-κBNLRP3 ligandsMortality rateAlveolar macrophagesDNA synthesisα-Synuclein Oligomers Induce Glutamate Release from Astrocytes and Excessive Extrasynaptic NMDAR Activity in Neurons, Thus Contributing to Synapse Loss
Trudler D, Sanz-Blasco S, Eisele Y, Ghatak S, Bodhinathan K, Akhtar M, Lynch W, Piña-Crespo J, Talantova M, Kelly J, Lipton S. α-Synuclein Oligomers Induce Glutamate Release from Astrocytes and Excessive Extrasynaptic NMDAR Activity in Neurons, Thus Contributing to Synapse Loss. Journal Of Neuroscience 2021, 41: 2264-2273. PMID: 33483428, PMCID: PMC8018774, DOI: 10.1523/jneurosci.1871-20.2020.Peer-Reviewed Original ResearchConceptsLewy body dementiaExtrasynaptic NMDA receptorsSynaptic damageParkinson's diseaseNeuronal lossLewy bodiesNMDAR activityDisease progressionΑSyn oligomersPotential disease-modifying interventionsNeurodegenerative diseasesΑ-synucleinExtrasynaptic NMDAR activitySynaptic NMDAR activityDisease-modifying interventionsPatch-clamp recordingsMajor neuropathological characteristicsSynaptic lossAstrocytic glutamateGlutamate releaseSynapse lossSpine lossExtrasynaptic NMDARsFemale miceHippocampal slices
2019
Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls
Ghatak S, Dolatabadi N, Trudler D, Zhang X, Wu Y, Mohata M, Ambasudhan R, Talantova M, Lipton S. Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. ELife 2019, 8: e50333. PMID: 31782729, PMCID: PMC6905854, DOI: 10.7554/elife.50333.Peer-Reviewed Original ResearchConceptsDisease brainNeuronal culturesHuman Alzheimer's disease brainCerebral organoidsAD-related mutationsHiPSC-derived neuronsTransgenic AD miceInhibitory synaptic activityMechanisms of hyperexcitabilityAlzheimer's disease brainAberrant electrical activitySodium current densityAD micePathophysiological correlatesSynaptic dysfunctionAD pathophysiologyExcessive excitabilitySynaptic activityObserved hyperexcitabilityCognitive declineBursting activityHyperexcitabilityPresenilin 1Electrical activityNeurite length
2014
Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice
Kesby J, Markou A, Semenova S, Grant I, Ellis R, Letendre S, Achim C, Woods S, Carr A, Letendre S, Ellis R, Schrier R, Heaton R, Atkinson J, Cherner M, Marcotte T, Morgan E, Brown G, Jernigan T, Dale A, Liu T, Scadeng M, Fennema-Notestine C, Archibald S, Achim C, Masliah E, Lipton S, Soontornniyomkij V, Gamst A, Cushman C, Abramson I, Vaida F, Deutsch R, Umlauf A, Atkinson J, Marquie-Beck J, Minassian A, Perry W, Geyer M, Henry B, Young J, Grethe A, Paulus M, Ellis R, Morris S, Smith D, Grant I, Semenova S, Markou A, Kesby J, Kaul M. Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice. European Neuropsychopharmacology 2014, 25: 141-150. PMID: 25476577, PMCID: PMC4289653, DOI: 10.1016/j.euroneuro.2014.07.014.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, OcularAnalysis of VarianceAnimalsBody WeightCentral Nervous System StimulantsCognition DisordersDisease Models, AnimalGene Expression RegulationGlial Fibrillary Acidic ProteinHIV Envelope Protein gp120MaleMaze LearningMethamphetamineMiceMice, Inbred C57BLMice, TransgenicReaction TimeRecognition, PsychologyConceptsGp120-tg miceCognitive domainsBarnes mazeMethamphetamine exposureCognitive deficitsSpatial learningAssociative recognition memoryDiscrete cognitive domainsMethamphetamine abuseHuman immunodeficiency virusRecognition memoryExecutive functionBarnes maze testCognitive performanceChronic methamphetamine exposureCognitive functionGp120 expressionAcquisition trialsGreater deficitsHIV infectionPlace testStrategy scoresNeurocognitive outcomesMethamphetamine usersSpatial strategies
2009
Molecular stages of rapid and uniform neuralization of human embryonic stem cells
Bajpai R, Coppola G, Kaul M, Talantova M, Cimadamore F, Nilbratt M, Geschwind D, Lipton S, Terskikh A. Molecular stages of rapid and uniform neuralization of human embryonic stem cells. Cell Death & Differentiation 2009, 16: 807-825. PMID: 19282867, PMCID: PMC3432273, DOI: 10.1038/cdd.2009.18.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsEmbryonic stem cellsNeural precursor cellsDynamic gene expression analysisStem cellsGene expression changesPrecursor cellsGene expression analysisEarly human developmentCoregulated genesPrimitive ectodermExpression analysisExpression changesMouse brainPotent oncogeneMolecular signalingUniform differentiationHuman biologyEfficient differentiationFuture cell-based therapiesFunctional neuronsNeuralizationPosterior markersNeonatal mouse brainNeural proliferation
2006
HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection
Kaul M, Ma Q, Medders K, Desai M, Lipton S. HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death & Differentiation 2006, 14: 296-305. PMID: 16841089, DOI: 10.1038/sj.cdd.4402006.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virus-1Neuronal cell deathStromal cell-derived factor-1HIV-1 envelope glycoprotein gp120Cell-derived factor-1Cell deathHIV-1 coreceptor CCR5Chemokine receptor CCR5Immunodeficiency virus-1Brain-derived cellsEnvelope glycoprotein gp120Intracellular free Ca2Gp120 neurotoxicityCCR5 ligandsHIV coreceptorsP38 mitogen-activated protein kinaseCCR5 agonistsNeuroprotective pathwaysReceptor CCR5Heterologous desensitizationCoreceptor CCR5CXCR4 agonistCCR5Glial culturesGlycoprotein gp120
2000
Expression of GABAC receptor ρ1 and ρ2 subunits during development of the mouse retina
Greka A, Lipton S, Zhang D. Expression of GABAC receptor ρ1 and ρ2 subunits during development of the mouse retina. European Journal Of Neuroscience 2000, 12: 3575-3582. PMID: 11029627, DOI: 10.1046/j.1460-9568.2000.00247.x.Peer-Reviewed Original ResearchConceptsRetinal developmentGamma-aminobutyric acid type C receptorMouse retinaRho subunitsReceptor-mediated currentsPostnatal day 6Type C receptorsBipolar cell differentiationMouse retinal developmentΡ2 subunitsBipolar cellsC receptorRho2 subunitsRho1 subunitDay 6ReceptorsEye openingSubunit transcriptionSubunit messageAdulthoodRetinaFuture studiesCompetitive PCRCell differentiationP9Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury
Li M, Ona V, Chen M, Kaul M, Tenneti L, Zhang X, Stieg P, Lipton S, Friedlander R. Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury. Neuroscience 2000, 99: 333-342. PMID: 10938439, DOI: 10.1016/s0306-4522(00)00173-1.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCord injuryCaspase-1Acute central nervous system insultLesion sizeCentral nervous system insultsTraumatic spinal cord injuryVehicle-treated miceSham-operated miceNervous system insultsCaspase-3Spinal cord samplesNon-neuronal cellsN-benzyloxycarbonyl-ValCaspase-1 activityCaspase-3 expressionCell deathNeurological dysfunctionCord samplesMotor functionTissue injuryMouse modelTherapeutic implicationsTransgenic miceTissue damage
1999
The contribution of various NOS gene products to HIV-1 coat protein (gp120)-mediated retinal ganglion cell injury.
Dreyer E, Zurakowski D, Gorla M, Vorwerk C, Lipton S. The contribution of various NOS gene products to HIV-1 coat protein (gp120)-mediated retinal ganglion cell injury. Investigative Ophthalmology & Visual Science 1999, 40: 983-9. PMID: 10102296.Peer-Reviewed Original ResearchConceptsNitric oxide synthaseHIV-1 coat proteinRetinal ganglion cell injuryIsoforms of NOSNitric oxideNeuronal nitric oxide synthaseGanglion cell injuryRetinal ganglion cellsPresence of nNOSNOS-deficient miceWild-type miceNeuronal lossExcitotoxic pathwayIntravitreal injectionGanglion cellsGp120 toxicityNeuronal pathologyNOS inhibitorOxide synthaseHIV-1Cell injuryControl animalsNervous systemGp120Pathologic statesMice Deficient in Mac-1 (CD11b/CD18) Are Less Susceptible to Cerebral Ischemia/Reperfusion Injury
Soriano S, Coxon A, Wang Y, Frosch M, Lipton S, Hickey P, Mayadas T. Mice Deficient in Mac-1 (CD11b/CD18) Are Less Susceptible to Cerebral Ischemia/Reperfusion Injury. Stroke 1999, 30: 134-139. PMID: 9880401, DOI: 10.1161/01.str.30.1.134.Peer-Reviewed Original ResearchConceptsTransient focal cerebral ischemiaRegional cerebral blood flowMac-1-deficient miceFocal cerebral ischemiaCerebral blood flowMac-1Cerebral ischemiaBrain sectionsBlood flowCerebral ischemia/reperfusion injuryFocal ischemia/reperfusionIschemia/reperfusion injuryLeft middle cerebral arteryCerebral cell deathLeukocyte beta2 integrinsIschemic brain tissueReperfusion-induced injuryMiddle cerebral arteryIschemia/reperfusionWild-type miceLaser Doppler flowmeterWild-type cohortsMac-1 deficiencyMacrophage-1 antigenInfarct volume
1998
Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A
Das S, Sasaki Y, Rothe T, Premkumar L, Takasu M, Crandall J, Dikkes P, Conner D, Rayudu P, Cheung W, Chen H, Lipton S, Nakanishi N. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 1998, 393: 377-381. PMID: 9620802, DOI: 10.1038/30748.Peer-Reviewed Original ResearchConceptsNMDA receptorsReceptor subunit NR1Synaptic refinementSpine densityNMDA receptor subunit NR3ANMDA responsesNMDA subclassSmall unitary conductanceNMDAR activitySubunit NR1NMDAR subunitsCerebrocortical neuronsDendritic spinesSynaptic plasticityNR1 subunitMice resultsSingle-channel recordingsGenetic knockoutSynaptic elementsHeteromultimeric channelsNR1NR3AXenopus oocytesUnitary conductanceNMDATissue plasminogen activator (tPA) increase neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice
Wang Y, Tsirka S, Strickland S, Stieg P, Soriano S, Lipton S. Tissue plasminogen activator (tPA) increase neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nature Medicine 1998, 4: 228-231. PMID: 9461198, DOI: 10.1038/nm0298-228.Peer-Reviewed Original ResearchConceptsTissue plasminogen activatorTPA-deficient miceWild-type miceCerebral infarctsNeuronal damageEffects of tPAIntravenous tissue plasminogen activatorRole of tPAPlasminogen activatorSmall cerebral infarctsAcute cerebral infarctsFocal cerebral ischemiaMiddle cerebral arteryIschemia/reperfusionStroke-induced injuryCerebral viabilityIntravascular filamentAcute strokeExcitotoxic damageCerebral ischemiaCerebral arteryLarge infarctsIntracerebral injectionIntravenous injectionThrombolytic agents
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply