2014
Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, Ghosh D, Kanyo J, Zhang Y, Seyb K, Ononenyi C, Foscue E, Anderson GM, Gresack J, Cuny GD, Glicksman MA, Greengard P, Lam TT, Tautz L, Nairn AC, Ellman JA, Lombroso PJ. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease. PLOS Biology 2014, 12: e1001923. PMID: 25093460, PMCID: PMC4122355, DOI: 10.1371/journal.pbio.1001923.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmino Acid SequenceAnimalsBenzothiepinsCatalytic DomainCell DeathCerebral CortexCognition DisordersCysteineDisease Models, AnimalEnzyme InhibitorsHigh-Throughput Screening AssaysHumansMaleMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronsPhosphorylationPhosphotyrosineProtein Tyrosine Phosphatases, Non-ReceptorSubstrate SpecificityConceptsInhibitors of stepsSpecificity of inhibitorsIsoxazolepropionic acid receptor (AMPAR) traffickingCatalytic cysteinePTP inhibitorsTyrosine phosphataseTyrosine phosphorylationSecondary assaysSTEP KO miceReceptor traffickingFirst large-scale effortN-methyl-D-aspartate receptorsPyk2 activitySTEP inhibitorLarge-scale effortsNovel therapeutic targetSynaptic functionAlzheimer's diseaseNeurodegenerative disordersCortical cellsTherapeutic targetERK1/2Specificity experimentsPhosphataseInhibitors
2013
Cocaine-Induced Changes of Synaptic Transmission in the Striatum are Modulated by Adenosine A2A Receptors and Involve the Tyrosine Phosphatase STEP
Chiodi V, Mallozzi C, Ferrante A, Chen JF, Lombroso PJ, Di Stasi AM, Popoli P, Domenici MR. Cocaine-Induced Changes of Synaptic Transmission in the Striatum are Modulated by Adenosine A2A Receptors and Involve the Tyrosine Phosphatase STEP. Neuropsychopharmacology 2013, 39: 569-578. PMID: 23989619, PMCID: PMC3895235, DOI: 10.1038/npp.2013.229.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCerebral CortexCocaineCorpus StriatumDopamine Uptake InhibitorsEnzyme InhibitorsGene Expression RegulationHumansIn Vitro TechniquesInhibitory Postsynaptic PotentialsMaleMiceMice, Inbred C57BLMice, KnockoutNeural PathwaysNeuronsProtein Tyrosine Phosphatases, Non-ReceptorReceptor, Adenosine A2ASynaptic TransmissionSynaptosomesVanadatesConceptsEffects of cocaineSynaptic transmissionAdenosine A2A receptorsStriatal-enriched protein tyrosine phosphatasePharmacological actionsA2A receptorsWhole-cell voltage-clamp recordingsA2AR antagonist ZM241385Excitatory post-synaptic currentsCocaine-induced reductionMedium spiny neuronsCocaine-induced changesVoltage-clamp recordingsPost-synaptic currentsA2AR knockout miceCorticostriatal slicesStriatal slicesPsychomotor effectsSpiny neuronsSynaptic mechanismsAntagonist ZM241385Synaptic depressionClamp recordingsBrain areasStriatum
2012
The tyrosine phosphatase STEP constrains amygdala-dependent memory formation and neuroplasticity
Olausson P, Venkitaramani D, Moran T, Salter M, Taylor J, Lombroso P. The tyrosine phosphatase STEP constrains amygdala-dependent memory formation and neuroplasticity. Neuroscience 2012, 225: 1-8. PMID: 22885232, PMCID: PMC3725644, DOI: 10.1016/j.neuroscience.2012.07.069.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaAnalysis of VarianceAnimalsBiophysicsConditioning, OperantElectric StimulationExcitatory Postsynaptic PotentialsFearMaleMAP Kinase Signaling SystemMemoryMiceMice, Inbred C57BLMice, TransgenicNeuronal PlasticityPatch-Clamp TechniquesProtein Tyrosine Phosphatases, Non-ReceptorReinforcement ScheduleReinforcement, PsychologyConceptsSynaptic plasticityExperience-dependent synaptic plasticityAspartic acid (NMDA) receptorsMemory formationLong-term potentiationAdult neuroplasticityAmygdala-dependent memory formationPharmacological treatmentKO miceExperience-induced neuroplasticityTyrosine phosphatase STEPNR2B subunitLateral amygdalaBrain regionsTyrosine kinase FynAcid receptorsStriatal-enriched protein tyrosine phosphataseNeuroplasticityMiceERK phosphorylationReceptor internalizationERK signalingKinase 1/2Detectable expressionSTEP KO miceThe tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications
Carty NC, Xu J, Kurup P, Brouillette J, Goebel-Goody SM, Austin DR, Yuan P, Chen G, Correa PR, Haroutunian V, Pittenger C, Lombroso PJ. The tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications. Translational Psychiatry 2012, 2: e137-e137. PMID: 22781170, PMCID: PMC3410627, DOI: 10.1038/tp.2012.63.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsSTEP61 levelsSurface expressionPostmortem anterior cingulate cortexGluN2B-containing N-methyl-D-aspartate receptorsGluN1/GluN2B receptorsMK-801 treatmentPathophysiology of schizophreniaAnterior cingulate cortexSTEP knockout miceDorsolateral prefrontal cortexChronic administrationChronic treatmentNeuroleptic treatmentAntipsychotic medicationGlutamatergic functionMK-801Glutamate hypothesisMedications resultsTyrosine phosphatase STEPGlutamatergic signalingKnockout miceGluN2B receptorsCingulate cortexSynaptic plasticity
2011
Striatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory
Venkitaramani DV, Moura PJ, Picciotto MR, Lombroso PJ. Striatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory. European Journal Of Neuroscience 2011, 33: 2288-2298. PMID: 21501258, PMCID: PMC3118976, DOI: 10.1111/j.1460-9568.2011.07687.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalFocal Adhesion Kinase 2HippocampusMemoryMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProtein Tyrosine Phosphatases, Non-ReceptorReceptors, AMPAReceptors, N-Methyl-D-AspartateSynaptic TransmissionConceptsStriatal-enriched protein tyrosine phosphataseSTEP KO miceProtein tyrosine phosphataseBrain-specific phosphataseProline-rich tyrosine kinaseEffect of deletionN-methyl-D-aspartate receptorsERK1/2 substratesNR1/NR2B N‐Methyl‐d‐Aspartate ReceptorsPotential molecular mechanismsTyrosine phosphataseSignaling proteinsTyrosine phosphorylationDownstream effectorsKinase 1/2Molecular mechanismsTyrosine kinaseFunctional importanceKnockout micePhosphorylationSTEP knockout miceSynaptic strengtheningIsoxazole propionic acid (AMPA) receptorsSynaptosomal expressionRegulation
2007
Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase
Choi YS, Lin SL, Lee B, Kurup P, Cho HY, Naegele JR, Lombroso PJ, Obrietan K. Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase. Journal Of Neuroscience 2007, 27: 2999-3009. PMID: 17360923, PMCID: PMC2701360, DOI: 10.1523/jneurosci.4913-06.2007.Peer-Reviewed Original ResearchConceptsStriatal-enriched protein tyrosine phosphataseERK/MAPK activationProtein tyrosine phosphataseCell deathTyrosine phosphataseExtracellular signal-regulated kinase/mitogen-activated protein kinase pathwayKinase/mitogen-activated protein kinase pathwayMAPK activationMAPK pathwayERK/MAPK signalingMitogen-activated protein kinase pathwayStriatal enriched protein tyrosine phosphataseProtein kinase pathwayNeuroprotective responseKinase pathwayImmediate early gene expressionKey regulatorMAPK signalingGene expressionMolecular mechanismsVivo disruptionSignificant rescuePathwayPhosphataseActivation