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
Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia
Deb I, Manhas N, Poddar R, Rajagopal S, Allan AM, Lombroso PJ, Rosenberg GA, Candelario-Jalil E, Paul S. Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia. Journal Of Neuroscience 2013, 33: 17814-17826. PMID: 24198371, PMCID: PMC3818554, DOI: 10.1523/jneurosci.2346-12.2013.Peer-Reviewed Original ResearchConceptsIschemic brain damageStriatal-enriched phosphataseBrain damageNeuroprotective roleBrain injuryP38 MAPK activationSustained p38 MAPK activationIschemic brain injuryFocal cerebral ischemiaOnset of reperfusionHypoxia-reoxygenation injuryP38 MAPKMAPK activationIschemic strokeNeurological deficitsCerebral ischemiaStroke therapyKO miceRat modelP38 MAPK pathwayCultured neuronsNeuronal culturesGenetic deletionSecondary activationInjuryCocaine-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
2009
Heterogeneity and Homogeneity Across the Autism Spectrum: The Role of Development
Lombroso P, Ogren M, Jones W, Klin A. Heterogeneity and Homogeneity Across the Autism Spectrum: The Role of Development. Journal Of The American Academy Of Child & Adolescent Psychiatry 2009, 48: 471-473. PMID: 19395902, DOI: 10.1097/chi.0b013e31819f6c0d.Peer-Reviewed Original Research
2008
The Tyrosine Phosphatase STEP Mediates AMPA Receptor Endocytosis after Metabotropic Glutamate Receptor Stimulation
Zhang Y, Venkitaramani DV, Gladding CM, Zhang Y, Kurup P, Molnar E, Collingridge GL, Lombroso PJ. The Tyrosine Phosphatase STEP Mediates AMPA Receptor Endocytosis after Metabotropic Glutamate Receptor Stimulation. Journal Of Neuroscience 2008, 28: 10561-10566. PMID: 18923032, PMCID: PMC2586105, DOI: 10.1523/jneurosci.2666-08.2008.Peer-Reviewed Original ResearchConceptsStriatal-enriched protein tyrosine phosphataseProtein tyrosine phosphataseTyrosine phosphataseAMPAR internalizationMitogen-activated protein kinasePhosphoinositide-3-kinase (PI3K) pathwayAMPA receptor endocytosisTyrosine dephosphorylationAMPA receptor traffickingReceptor endocytosisProtein kinaseKinase pathwayStimulation of mGluR5Receptor traffickingNMDAR endocytosisAMPAR traffickingEndocytosisMetabotropic glutamate receptor stimulationTraffickingSurface expressionInternalizationGlutamate receptor stimulationSynaptic plasticityCentral eventPhosphatase
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
2001
Genetics of Childhood Disorders: XXXI. Autoimmune Disorders, Part 4: Is Sydenham Chorea an Autoimmune Disorder?
LOISELLE C, SINGER H, Lombroso P. Genetics of Childhood Disorders: XXXI. Autoimmune Disorders, Part 4: Is Sydenham Chorea an Autoimmune Disorder? Journal Of The American Academy Of Child & Adolescent Psychiatry 2001, 40: 1234-1236. PMID: 11589538, DOI: 10.1097/00004583-200110000-00019.Peer-Reviewed Original ResearchAntibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders
Morshed S, Parveen S, Leckman J, Mercadante M, Kiss M, Miguel E, Arman A, Yazgan Y, Fujii T, Paul S, Peterson B, Zhang H, King R, Scahill L, Lombroso P. Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders. Biological Psychiatry 2001, 50: 566-577. PMID: 11690591, DOI: 10.1016/s0006-3223(01)01096-4.Peer-Reviewed Original ResearchConceptsTotal antinuclear antibodiesAntinuclear antibodiesAutoimmune disordersTourette syndromeAnticytoskeletal antibodiesAntineural antibodiesStreptococcal infectionT patientsTS patientsBeta-hemolytic streptococcal infectionPrior streptococcal infectionHemolytic streptococcal infectionAntistreptolysin O titerIndirect immunofluorescent assayLevels of immunoreactivityWestern blot techniqueMean rankClinical characteristicsSydenham's choreaO titerPatient groupSC patientsIgG antibodiesIgG classNormal controlsThermal Sensitivity in Tourette Syndrome: Preliminary Report
Scahill L, Lombroso P, Mack G, Van Wattum P, Zhang H, Vitale A, Leckman J. Thermal Sensitivity in Tourette Syndrome: Preliminary Report. Perceptual And Motor Skills 2001, 92: 419-432. PMID: 11361302, DOI: 10.2466/pms.2001.92.2.419.Peer-Reviewed Original ResearchConceptsTourette syndromeSubgroup of patientsAge of onsetAdult male subjectsCurrent ageTic symptomsDopaminergic pathwaysSex distributionCurrent severityMale subjectsMean differenceSyndromeControl periodPreliminary reportSweat rateAgeSymptomsSubjectsOverall courseDegrees COnsetPatientsIllnessSeverityCourse
2000
Genetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function
ARNSTEN A, Lombroso P. Genetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function. Journal Of The American Academy Of Child & Adolescent Psychiatry 2000, 39: 1201-1203. PMID: 10986819, DOI: 10.1097/00004583-200009000-00022.Peer-Reviewed Original ResearchThe Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway
Paul S, Snyder G, Yokakura H, Picciotto M, Nairn A, Lombroso P. The Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway. Journal Of Neuroscience 2000, 20: 5630-5638. PMID: 10908600, PMCID: PMC6772528, DOI: 10.1523/jneurosci.20-15-05630.2000.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalytic DomainCorpus StriatumCyclic AMP-Dependent Protein KinasesEnzyme ActivationIn Vitro TechniquesMaleMolecular Sequence DataNeuronsPhosphoproteinsPhosphorus RadioisotopesPhosphorylationProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, Dopamine D1Signal TransductionConceptsProtein tyrosine phosphatase familyCAMP-dependent protein kinaseTryptic phosphopeptide mappingPotential phosphorylation sitesUnique N-terminalProtein-protein interactionsMembrane-associated proteinsRole of phosphorylationTyrosine phosphatase familyAmino acid sequenceSite-directed mutagenesisAmino acid sequencingPKA-dependent pathwayTyrosine phosphatase STEPPhosphatase familyPhosphopeptide mappingPhosphorylation sitesAlternative splicingSubcellular compartmentsProtein kinaseTerminal domainEquivalent residuesCytosolic proteinsSpecific residuesAcid sequenceGenetics of Childhood Disorders: XVI. Angelman Syndrome: A Failure to Process
LOMBROSO P, Lombroso P. Genetics of Childhood Disorders: XVI. Angelman Syndrome: A Failure to Process. Journal Of The American Academy Of Child & Adolescent Psychiatry 2000, 39: 931-933. PMID: 10892237, DOI: 10.1097/00004583-200007000-00024.Peer-Reviewed Original Research
1999
Genetics of Childhood Disorders: IV. Linkage Analysis
Lombroso P, PAULS D. Genetics of Childhood Disorders: IV. Linkage Analysis. Journal Of The American Academy Of Child & Adolescent Psychiatry 1999, 38: 932-934. PMID: 10405513, DOI: 10.1097/00004583-199907000-00025.Peer-Reviewed Original ResearchDevelopment of the Cerebral Cortex: XIV. Stress Impairs Prefrontal Cortical Function
Lombroso P, ARNSTEN A. Development of the Cerebral Cortex: XIV. Stress Impairs Prefrontal Cortical Function. Journal Of The American Academy Of Child & Adolescent Psychiatry 1999, 38: 220-222. PMID: 9951224, DOI: 10.1097/00004583-199902000-00024.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1995
Risperidone Treatment of Children and Adolescents with Chronic Tic Disorders: A Preliminary Report
LOMBROSO P, SCAHILL L, KING R, LYNCH K, CHAPPELL P, PETERSON B, McDOUGLE C, LECKMAN J. Risperidone Treatment of Children and Adolescents with Chronic Tic Disorders: A Preliminary Report. Journal Of The American Academy Of Child & Adolescent Psychiatry 1995, 34: 1147-1152. PMID: 7559308, DOI: 10.1097/00004583-199509000-00011.Peer-Reviewed Original ResearchConceptsChronic tic disorderTic disordersObsessive-compulsive disorderChronic motor tic disorderYale Global Tic Severity ScaleDopamine-blocking propertiesOpen-label trialFrequent side effectsEfficacy of risperidoneMotor tic disorderShort-term safetyTic Severity ScaleComorbid obsessive-compulsive disorderYale-Brown Obsessive Compulsive ScaleObsessive Compulsive ScaleClinical responseRisperidone treatmentMean ageTic scoreSeverity ScaleSide effectsTourette syndromeComorbid diagnosesTic frequencyWeight gain
1993
A protein tyrosine phosphatase expressed within dopaminoceptive neurons of the basal ganglia and related structures
Lombroso P, Naegele, Sharma E, Lerner M. A protein tyrosine phosphatase expressed within dopaminoceptive neurons of the basal ganglia and related structures. Journal Of Neuroscience 1993, 13: 3064-3074. PMID: 8331384, PMCID: PMC6576687, DOI: 10.1523/jneurosci.13-07-03064.1993.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasal GangliaBase SequenceBlotting, WesternBrainChromatography, AffinityCorpus StriatumDopamine and cAMP-Regulated Phosphoprotein 32FemaleGene ExpressionImmune SeraImmunohistochemistryKineticsMaleMolecular Sequence DataMolecular WeightNerve Tissue ProteinsNeuronsOligodeoxyribonucleotidesOligonucleotides, AntisenseOrgan SpecificityPhosphoproteinsPolymerase Chain ReactionProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorRatsReceptors, DopamineRecombinant Fusion Proteins
1991
Emergence of Self-Destructive Phenomena in Children and Adolescents during Fluoxetine Treatment
KING R, RIDDLE M, CHAPPELL P, HARDIN M, ANDERSON G, LOMBROSO P, SCAHILL L. Emergence of Self-Destructive Phenomena in Children and Adolescents during Fluoxetine Treatment. Journal Of The American Academy Of Child & Adolescent Psychiatry 1991, 30: 179-186. PMID: 2016219, DOI: 10.1097/00004583-199103000-00003.Peer-Reviewed Original ResearchConceptsFluoxetine treatmentObsessive-compulsive disorderUniversity Clinical Research CenterClinical Research CenterMajor risk factorDrug-induced activationPrior suicidal ideationYounger patientsRisk factorsRegulation of aggressionPatientsSuicidal ideationSelf-destructive behaviorFluoxetineAge 10Apparent associationVulnerable individualsDisordersTreatmentIdeationDe novoHospitalizationSymptoms