2020
Chapter 39 Obsessive–compulsive disorder
Bloch M, Artukoglu B, Lennington J, Szuhay G, Lombroso P. Chapter 39 Obsessive–compulsive disorder. 2020, 663-674. DOI: 10.1016/b978-0-12-813866-3.00039-4.Peer-Reviewed Original ResearchObsessive-compulsive disorderEvidence-based treatmentsCognitive behavioral therapyTreatment-refractory obsessive-compulsive disorderSignificant hereditary componentRepetitive transcranial magnetic stimulationTranscranial magnetic stimulationBrain stimulantBehavioral therapyMagnetic stimulationCortico-striatoSelective serotonin reuptake inhibitorsPharmacological treatment strategiesFirst-line treatmentSerotonin reuptake inhibitorsAntipsychotic augmentationGenetic risk factorsReuptake inhibitorsDisordersRisk factorsTreatment strategiesAnimal studiesNeuroimagingModulating agentsHereditary componentChapter 40 Tourette syndrome
Fasching L, Brady M, Bloch M, Lombroso P, Vaccarino F. Chapter 40 Tourette syndrome. 2020, 675-686. DOI: 10.1016/b978-0-12-813866-3.00040-0.ChaptersTourette syndromeThalamic-cortical circuitryHuman postmortem brain tissueThalamo-cortical circuitryAdult TS patientsStriatal volume lossPostmortem brain tissueEnvironmental risk factorsStriatal interneuronsDopaminergic receptorsRecurrence rateAmeliorate symptomsBasal gangliaRisk factorsFamilial recurrence ratePharmacological strategiesVocal ticsTS patientsAnimal modelsMetabolic hypofunctionComplex neuropsychiatric disorderBrain tissueMolecular abnormalitiesNeuropsychiatric disordersGenetic alterations
2018
Striatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2018, 5188-5203. DOI: 10.1007/978-3-319-67199-4_630.Peer-Reviewed Original Research
2016
Striatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2016, 1-16. DOI: 10.1007/978-1-4614-6438-9_630-1.Peer-Reviewed Original Research
2015
ChemInform Abstract: Synthesis of Benzopentathiepin Analogues and Their Evaluation as Inhibitors of the Phosphatase STEP.
Baguley T, Nairn A, Lombroso P, Ellman J. ChemInform Abstract: Synthesis of Benzopentathiepin Analogues and Their Evaluation as Inhibitors of the Phosphatase STEP. ChemInform 2015, 46: no-no. DOI: 10.1002/chin.201526245.Peer-Reviewed Original ResearchChapter 106 Obsessive–Compulsive Disorder
Bloch M, Lennington J, Szuhay G, Lombroso P. Chapter 106 Obsessive–Compulsive Disorder. 2015, 1301-1310. DOI: 10.1016/b978-0-12-410529-4.00106-6.Peer-Reviewed Original ResearchObsessive-compulsive disorderEvidence-based treatmentsTreatment-refractory obsessive-compulsive disorderSignificant hereditary componentRepetitive transcranial magnetic stimulationTranscranial magnetic stimulationThalamo-cortical circuitsMagnetic stimulationCortico-striatoSelective serotonin reuptake inhibitorsPharmacological treatment strategiesSerotonin reuptake inhibitorsAntipsychotic augmentationGenetic risk factorsReuptake inhibitorsDisordersRisk factorsTreatment strategiesAnimal studiesModulating agentsNeuroimagingHereditary componentCompulsionDeep brainObsessionChapter 107 Tourette Syndrome
Lennington J, Bloch M, Scahill L, Szuhay G, Lombroso P, Vaccarino F. Chapter 107 Tourette Syndrome. 2015, 1311-1320. DOI: 10.1016/b978-0-12-410529-4.00107-8.ChaptersTourette syndromeThalamic-cortical circuitryChildhood-onset neuropsychiatric disorderBasal ganglia circuitryStriatal interneuronsAmeliorate symptomsBasal gangliaPharmacological strategiesVocal ticsAnimal modelsPostmortem tissueNeuropsychiatric disordersSyndromeContemporary treatmentHeterogeneous disorderLarge genome-wide association studiesRecent screeningDysfunctionPotential target sitesStereotypic behaviorDisordersGenome-wide association studiesAssociation studiesChemical disruptionDopaminergic
2014
Correction to Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase
Baguley T, Xu H, Chatterjee M, Nairn A, Lombroso P, Ellman J. Correction to Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase. Journal Of Medicinal Chemistry 2014, 57: 10564-10564. PMCID: PMC4364512, DOI: 10.1021/jm5018847.Peer-Reviewed Original ResearchInhibitor 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 activationInjurySubstrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase
Baguley TD, Xu HC, Chatterjee M, Nairn AC, Lombroso PJ, Ellman JA. Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase. Journal Of Medicinal Chemistry 2013, 56: 7636-7650. PMID: 24083656, PMCID: PMC3875168, DOI: 10.1021/jm401037h.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiphenyl CompoundsBlood-Brain BarrierBoronic AcidsCells, CulturedCerebral CortexHumansNeuronsPermeabilityPhosphorous AcidsProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleySmall Molecule LibrariesStereoisomerismStructure-Activity RelationshipSubstrate SpecificityConceptsSubstrate Activity ScreeningProtein tyrosine phosphatase activityProtein tyrosine phosphataseTyrosine phosphatase activityGlutamate receptor internalizationOptimization of fragmentsTyrosine phosphataseDual specificityReceptor internalizationDevelopment of SelectiveSTEP inhibitorPhosphatase activityAlzheimer's diseaseIonotropic glutamate receptorsSubstrate-based approachNonpeptidic inhibitorsPotential targetAD mouse modelDrug discoveryRat cortical neuronsActivity screeningCortical neuronsGlutamate receptorsMouse modelNeuropsychiatric disordersCocaine-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 plasticityCalpain and STriatal-Enriched protein tyrosine Phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model
Gladding CM, Sepers MD, Xu J, Zhang LY, Milnerwood AJ, Lombroso PJ, Raymond LA. Calpain and STriatal-Enriched protein tyrosine Phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model. Human Molecular Genetics 2012, 21: 3739-3752. PMID: 22523092, PMCID: PMC3412376, DOI: 10.1093/hmg/dds154.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalpainCoculture TechniquesDisease Models, AnimalEnzyme ActivationEnzyme InhibitorsHuntington DiseaseIon Channel GatingMiceModels, BiologicalNeostriatumNeuronsPhosphorylationPhosphotyrosineProtein TransportProtein Tyrosine Phosphatases, Non-ReceptorReceptors, N-Methyl-D-AspartateSynapsesConceptsYAC128 striatumProtein tyrosine phosphatase activationNMDAR localizationCalpain cleavageProtein tyrosine phosphataseTyrosine phosphatase activationEarly synaptic defectsWhole-cell NMDAR currentsDisease mouse modelGluN2B expressionNMDA receptor traffickingMutant huntingtin proteinCalpain inhibitionTyrosine phosphataseHuntington's diseaseFull-length mhttPlasma membranePhosphatase activationC-terminusReceptor traffickingNMDAR traffickingPolyglutamine repeatsMouse modelHuntingtin proteinNMDA receptor localizationGenetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model
Goebel‐Goody S, Wilson‐Wallis E, Royston S, Tagliatela S, Naegele J, Lombroso P. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. Genes Brain & Behavior 2012, 11: 586-600. PMID: 22405502, PMCID: PMC3922131, DOI: 10.1111/j.1601-183x.2012.00781.x.Peer-Reviewed Original ResearchConceptsFragile X syndromeFragile X syndrome mouse modelProtein tyrosine phosphataseMental retardation proteinMRNAs downstreamControl translationTyrosine phosphataseGenetic manipulationGenetic basisFMR1 geneLoss of stepsX syndromeSyndrome mouse modelFMRPReceptor activationGlutamate receptor activationExcess levelsSynaptic strengthSynaptic strengtheningBasal levelsC-Fos activationActivationTranscriptionFynMouse modelInhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Tautz L, Sergienko E, Xu J, Liu W, Dahl R, Critton D, Su Y, Brown B, Chan X, Yang L, Bobkova E, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford N, Chung T, Mustelin T, Page R, Lombroso P. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. The FASEB Journal 2012, 26: 766.12-766.12. DOI: 10.1096/fasebj.26.1_supplement.766.12.Peer-Reviewed Original ResearchHematopoietic protein tyrosine phosphataseP38 activationProtein tyrosine phosphataseUnique amino acid residuesAmino acid residuesNew drug targetsCell cycle arrestMAP kinases ERK1/2Activation of ERK1/2Tyrosine phosphataseHePTPMutagenesis experimentsMAP kinaseKinases ERK1/2Acid residuesCatalytic pocketDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaERK1/2Prolonged activationHuman T cellsPharmacological inhibitionCancer cellsStriatal-Enriched Protein Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein Tyrosine Phosphatase (STEP). 2012, 1793-1804. DOI: 10.1007/978-1-4419-0461-4_630.Peer-Reviewed Original Research
2011
Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders
Goebel-Goody SM, Baum M, Paspalas CD, Fernandez SM, Carty NC, Kurup P, Lombroso PJ. Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders. Pharmacological Reviews 2011, 64: 65-87. PMID: 22090472, PMCID: PMC3250079, DOI: 10.1124/pr.110.003053.Peer-Reviewed Original ResearchConceptsStriatal-enriched protein tyrosine phosphataseProtein tyrosine phosphataseTyrosine phosphataseStress-activated protein kinase p38Extracellular regulated kinases 1Brain-specific phosphataseSrc family tyrosine kinase FynProtein kinase p38Tyrosine kinase FynN-methyl-D-aspartate receptorsFragile X syndromeDephosphorylation of ERK1/2Stroke/ischemiaSurface NMDARsKinase FynAlcohol-induced memory lossDiverse neuropsychiatric disordersLocal translationKinase 1Kinase p38STEP expressionX syndromeNeuronal functionDephosphorylationFunction contributesStriatal-Enriched Protein Tyrosine Phosphatase Expression and Activity in Huntington's Disease: A STEP in the Resistance to Excitotoxicity
Saavedra A, Giralt A, Rué L, Xifró X, Xu J, Ortega Z, Lucas JJ, Lombroso PJ, Alberch J, Pérez-Navarro E. Striatal-Enriched Protein Tyrosine Phosphatase Expression and Activity in Huntington's Disease: A STEP in the Resistance to Excitotoxicity. Journal Of Neuroscience 2011, 31: 8150-8162. PMID: 21632937, PMCID: PMC3472648, DOI: 10.1523/jneurosci.3446-10.2011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCalcineurinCell DeathDisease Models, AnimalGene Expression RegulationGene Products, tatHuntingtin ProteinHuntington DiseaseMiceMice, Neurologic MutantsMice, TransgenicMicroinjectionsNerve Tissue ProteinsNuclear ProteinsPhosphorylationProtein Tyrosine Phosphatases, Non-ReceptorQuinolinic AcidSignal TransductionConceptsStriatal-enriched protein tyrosine phosphataseCell deathSTEP expressionPhosphorylation levelsProtein Tyrosine Phosphatase ExpressionProtein tyrosine phosphataseSTEP phosphorylationTyrosine phosphataseProtein kinasePhosphorylated ERK2Phosphatase expressionHuntington's diseaseSTEP proteinMutant huntingtinCalcineurin activityPhosphorylationExon 1STEP protein levelsDisease mouse modelProtein levelsMouse modelMouse striatumTAT-STEPHuntington's disease mouse modelExpression