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 experimentsPhosphataseInhibitorsInhibition of striatal‐enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption
Darcq E, Hamida SB, Wu S, Phamluong K, Kharazia V, Xu J, Lombroso P, Ron D. Inhibition of striatal‐enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption. Journal Of Neurochemistry 2014, 129: 1024-1034. PMID: 24588427, PMCID: PMC4055745, DOI: 10.1111/jnc.12701.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAnimalsAntibodies, BlockingBlotting, WesternChoice BehaviorDown-RegulationEnzyme InhibitorsGene Knockdown TechniquesImmunohistochemistryLentivirusMaleMiceMice, Inbred C57BLMotor ActivityNeostriatumPhosphorylationProtein Tyrosine PhosphatasesQuinineRNA, Small InterferingSaccharin
2012
Calpain 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 localizationStriatal-Enriched Protein Tyrosine Phosphatase in Alzheimer’s Disease
Xu J, Kurup P, Nairn AC, Lombroso PJ. Striatal-Enriched Protein Tyrosine Phosphatase in Alzheimer’s Disease. Advances In Pharmacology 2012, 64: 303-325. PMID: 22840751, PMCID: PMC3740556, DOI: 10.1016/b978-0-12-394816-8.00009-x.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseNeurofibrillary tanglesStriatal-enriched protein tyrosine phosphataseAmyloid plaquesTreatment of ADHyperphosphorylated tau proteinSubstantial economic burdenProgressive diseasePotential clinical applicationsClinical symptomsBeta amyloidGlutamate receptorsEconomic burdenTau proteinCortical accumulationCognitive functionMemory lossBeneficial effectsDiseaseNeuronal membranesCommon formMultiple intracellularMillions of peopleClinical applicationImportant target
2011
Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Sergienko E, Xu J, Liu WH, Dahl R, Critton DA, Su Y, Brown BT, Chan X, Yang L, Bobkova EV, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford ND, Chung TD, Mustelin T, Page R, Lombroso PJ, Tautz L. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. ACS Chemical Biology 2011, 7: 367-377. PMID: 22070201, PMCID: PMC3288537, DOI: 10.1021/cb2004274.Peer-Reviewed Original ResearchConceptsHematopoietic protein tyrosine phosphataseP38 activationMitogen-activated protein kinases ERK1/2Protein tyrosine phosphataseUnique amino acid residuesSmall molecule modulatorsProtein kinases ERK1/2Amino acid residuesRegulation of MAPKNew drug targetsCell cycle arrestTyrosine phosphataseHePTPMutagenesis experimentsKinases ERK1/2Acid residuesCatalytic pocketCell senescenceDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaHematopoietic cellsERK1/2Prolonged activation
2010
Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model
Zhang Y, Kurup P, Xu J, Carty N, Fernandez SM, Nygaard HB, Pittenger C, Greengard P, Strittmatter SM, Nairn AC, Lombroso PJ. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 19014-19019. PMID: 20956308, PMCID: PMC2973892, DOI: 10.1073/pnas.1013543107.Peer-Reviewed Original ResearchConceptsStriatal-enriched tyrosine phosphataseTyrosine phosphataseDisease mouse modelStriatal-enriched phosphataseAlzheimer's diseaseCellular deficitsGenetic manipulationNMDA receptorsMouse modelTriple transgenic AD mouse modelIncurable neurodegenerative disorderTransgenic AD mouse modelAlzheimer's disease mouse modelPathophysiology of ADSTEP inhibitorGenetic reductionAD mouse modelHuman AD patientsSoluble Aβ oligomersSynaptic functionPhosphataseNeurodegenerative disordersAD patientsDevastating disorderAnimal models