2017
Combined HMG-COA reductase and prenylation inhibition in treatment of CCM
Nishimura S, Mishra-Gorur K, Park J, Surovtseva YV, Sebti SM, Levchenko A, Louvi A, Gunel M. Combined HMG-COA reductase and prenylation inhibition in treatment of CCM. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 5503-5508. PMID: 28500274, PMCID: PMC5448170, DOI: 10.1073/pnas.1702942114.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesDiphosphonatesDrosophilaDrug Evaluation, PreclinicalDrug Therapy, CombinationEndothelial CellsFatty Acids, MonounsaturatedFemaleFluvastatinHemangioma, Cavernous, Central Nervous SystemHigh-Throughput Screening AssaysHydroxymethylglutaryl-CoA Reductase InhibitorsImidazolesIndolesMaleMAP Kinase Signaling SystemMicePregnancyProtein PrenylationZoledronic AcidConceptsCerebral cavernous malformationsTreatment of CCMsCommon vascular anomaliesPotential pharmacological treatment optionsFocal neurological deficitsPharmacological treatment optionsCCM diseaseAcute mouse modelCentral nervous systemNeurological deficitsHemorrhagic strokePharmacological therapyLesion burdenVascular deficitsSymptomatic lesionsCombination therapyTreatment optionsVascular anomaliesGlial cellsCavernous malformationsMouse modelPrimary astrocytesNervous systemDrug AdministrationSustained inhibition
2016
B-Cell Depletion Reduces the Maturation of Cerebral Cavernous Malformations in Murine Models
Shi C, Shenkar R, Zeineddine HA, Girard R, Fam MD, Austin C, Moore T, Lightle R, Zhang L, Wu M, Cao Y, Gunel M, Louvi A, Rorrer A, Gallione C, Marchuk DA, Awad IA. B-Cell Depletion Reduces the Maturation of Cerebral Cavernous Malformations in Murine Models. Journal Of Neuroimmune Pharmacology 2016, 11: 369-377. PMID: 27086141, PMCID: PMC6746226, DOI: 10.1007/s11481-016-9670-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCentral Nervous System NeoplasmsDisease Models, AnimalFemaleHemangioma, Cavernous, Central Nervous SystemMaleMiceMice, TransgenicConceptsB-cell depletionCerebral cavernous malformationsCCM lesionsB cellsImmune responseMurine modelCavernous malformationsIron depositionB cell clonal expansionInflammatory cell infiltrationStage 2 lesionsProgression of lesionsBlood degradation productsCommon vascular malformationsPotential therapeutic agentROCK activityRho-kinase activityUntreated miceAntigenic triggerCell depletionCell infiltrationVascular malformationsImmune complexesTherapeutic benefitLesion genesis
2015
Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex
Fisher OS, Deng H, Liu D, Zhang Y, Wei R, Deng Y, Zhang F, Louvi A, Turk BE, Boggon TJ, Su B. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex. Nature Communications 2015, 6: 7937. PMID: 26235885, PMCID: PMC4526114, DOI: 10.1038/ncomms8937.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBlood VesselsCapillary PermeabilityCerebrovascular CirculationCrystallizationHemangioma, Cavernous, Central Nervous SystemIntracranial HemorrhagesMAP Kinase Kinase Kinase 3MiceMice, KnockoutMicrofilament ProteinsNeovascularization, PhysiologicRho GTP-Binding ProteinsRho-Associated KinasesSignal Transduction
2014
Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration
Louvi A, Nishimura S, Günel M. Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration. Development 2014, 141: 1404-1415. PMID: 24595293, PMCID: PMC3943187, DOI: 10.1242/dev.093526.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCell MovementCell ProliferationCyclin-Dependent Kinase 5FemaleHemangioma, Cavernous, Central Nervous SystemIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMice, TransgenicNeocortexNeural Stem CellsNeurogliaPregnancyRho GTP-Binding ProteinsRhoA GTP-Binding ProteinSignal TransductionConceptsCerebral cavernous malformation 3Neuronal migrationCerebral cavernous malformationsRadial glia progenitorsCell non-autonomous functionCerebrovascular disordersPyramidal neuronsCortical plateLaminar positioningSubventricular zoneCortical developmentCavernous malformationsRadial gliaLoss of functionNascent neuronsNeuronal morphologySevere malformationsGlia progenitorsNeural progenitorsNeuronsNon-autonomous functionsMalformationsRhoA pathwayPossible interactionsGlia
2011
Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology
Louvi A, Chen L, Two AM, Zhang H, Min W, Günel M. Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 3737-3742. PMID: 21321212, PMCID: PMC3048113, DOI: 10.1073/pnas.1012617108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsAstrocytesBlood VesselsCell ProliferationCell SurvivalGlial Fibrillary Acidic ProteinHemangioma, Cavernous, Central Nervous SystemMembrane ProteinsMiceMice, Neurologic MutantsNeurogliaPhenotypeSequence Analysis, RNAConceptsNeural cellsCerebral cavernous malformationsCell-nonautonomous mechanismsPathogenesis of CCMsRho GTPase signalingCell-autonomous mechanismsCell-autonomous roleCerebral cavernous malformation 3Cell death 10Central nervous systemConditional mouse mutantsNonautonomous functionsCytoskeletal remodelingRNA sequencingCCM3/Mouse mutantsNeurovascular unitNonautonomous mechanismsProper developmentVascular lesionsGene 1Function mutationsNervous systemAutonomous mechanismsLate functions
2009
Apoptotic Functions of PDCD10/CCM3, the Gene Mutated in Cerebral Cavernous Malformation 3
Chen L, Tanriover G, Yano H, Friedlander R, Louvi A, Gunel M. Apoptotic Functions of PDCD10/CCM3, the Gene Mutated in Cerebral Cavernous Malformation 3. Stroke 2009, 40: 1474-1481. PMID: 19246713, PMCID: PMC2709460, DOI: 10.1161/strokeaha.108.527135.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisApoptosis Regulatory ProteinsCaspase 3Central Nervous System NeoplasmsCulture Media, Serum-FreeEndothelial CellsGene Expression Regulation, NeoplasticHeLa CellsHemangioma, Cavernous, Central Nervous SystemHumansIn Situ Nick-End LabelingMembrane ProteinsMutationP38 Mitogen-Activated Protein KinasesProto-Oncogene ProteinsRNA, Small InterferingTransfectionUmbilical Veins