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
2022
S-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
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
2000
Functional 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
1997
Enhanced neuronal death from focal ischemia in AMPA-receptor transgenic mice
Le D, Das S, Wang Y, Yoshizawa T, Sasaki Y, Takasu M, Nemes A, Mendelsohn M, Dikkes P, Lipton S, Nakanishi N. Enhanced neuronal death from focal ischemia in AMPA-receptor transgenic mice. Brain Research 1997, 52: 235-241. PMID: 9495544, DOI: 10.1016/s0169-328x(97)00261-1.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBrainCell DeathCerebral CortexCrosses, GeneticDisease SusceptibilityFemaleGenetic VariationHeterozygoteIschemic Attack, TransientMaleMiceMice, Inbred C57BLMice, Inbred CBAMice, TransgenicNeocortexNeuronsPolymerase Chain ReactionReceptors, AMPATranscription, GeneticConceptsNeuronal cell deathMiddle cerebral arteryWild-type neuronsTransgenic miceAMPA receptorsCerebral ischemiaFocal ischemiaGluR2 flipExcitatory amino acid receptorsCell deathAcute cerebral ischemiaGlobal cerebral ischemiaAmino acid receptorsAMPAR-mediated currentsGlutamate receptor antagonistsPermanent focal ischemiaGenetic mouse modelsWild-type controlsExcitotoxic damageEAA receptorsLarge infarctionCerebral arteryFocal strokeGlutamate excitotoxicityNeuronal death
1994
HIV displays its coat of arms
Lipton S. HIV displays its coat of arms. Nature 1994, 367: 113-114. PMID: 8114907, DOI: 10.1038/367113a0.Peer-Reviewed Original Research
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