grant
Selective Inhibition of GRP 94 to Treat Ocular Hypertension and Glaucoma
Organization UNIVERSITY OF NOTRE DAMELocation NOTRE DAME, UNITED STATESPosted 1 Jul 2024Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY2025AD dementiaAccelerationAdolescentAdolescent YouthAgeAlzheimer Type DementiaAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's DiseaseAlzheimers DementiaAnteriorAqueous HumorBindingBiochemicalBiologicalBlindnessBody TissuesCell BodyCell Culture TechniquesCell DeathCell modelCellsCellular StressCellular Stress ResponseCellular modelChaperoneClientClinicCollaborationsComplexCranial Nerve IICrystallizationDNA mutationDataDegenerative Neurologic DisordersDevelopmentDiseaseDisorderDoseDrugsDysfunctionER stressEndoplasmic ReticulumErgastoplasmExhibitsEyeEyeballFunctional disorderGRPGRP geneGenetic ChangeGenetic defectGenetic mutationGlaucomaGoalsHealthHeat ShockHeat-Shock ReactionHeat-Shock ResponseHomolog of Drosophila TOLLHumanIn VitroIntraocular FluidIntraocular PressureIsoformsLeadLinkLytotoxicityMedicationMiceMice MammalsModelingModern ManMolecular ChaperonesMolecular InteractionMolecular TargetMurineMusMutateMutationNerve CellsNerve UnitNervous System Degenerative DiseasesNeural CellNeural Degenerative DiseasesNeural degenerative DisordersNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeuronsOcular HypertensionOcular TensionOptic NerveOutcomePOAGParalysis AgitansParkinsonParkinson DiseasePatientsPb elementPerfusionPersonsPharmaceutical PreparationsPhenotypePhysiologic Intraocular PressurePhysiopathologyPrimary Open Angle GlaucomaPrimary ParkinsonismPrimary Senile Degenerative DementiaProceduresProtein IsoformsProteinsPublishingRetinaRetinal Ganglion CellsRisk FactorsRodent ModelRoleSecond Cranial NerveSteroid CompoundSteroidsStructureStructure-Activity RelationshipSymptomsSystemTLR4TLR4 geneTestingTherapeuticTissuesToll HomologueToxic effectToxicitiesTrabecular MeshworkTrabecular meshwork structureTranslatingUnited StatesValidationaberrant protein foldingabnormal protein foldingage associatedage correlatedage dependentage linkedage relatedage specificagesanalogbiologiccell culturecell culturescell stresschemical structure functioncytotoxiccytotoxicitydegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdetermine efficacydevelopmentaldrug/agentefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationendoplasmic reticulum stressevaluate efficacyexamine efficacygain of functiongenome mutationglaucomatousheavy metal Pbheavy metal leadimprovedin vitro Assayin vivoinhibitorinsightintra-ocular pressurejuvenilejuvenile humanmouse modelmurine modelmutantmyocilinnecrocytosisnerve damageneurodegenerative illnessneuronalnew approachesnovel approachesnovel strategiesnovel strategyocular hypertensivepathologic protein foldingpathophysiologypre-clinical assessmentpreclinical assessmentpreventpreventingprimary degenerative dementiaprotein homeostasisprotein misfoldingproteostasisretinal ganglionscreeningscreeningssenile dementia of the Alzheimer typesmall molecular inhibitorsmall molecule inhibitorsocial rolestructure function relationshiptherapeutic targettoll-like receptor 4validationsvision lossvisual loss
Description preview
Project Summary
The accumulation of mutant myocillin leads to decreased aqueous humor outflow and results in ER
dysfunction. Grp94 is a major chaperone localized to the ER that is responsible for modulating ER stress and
the folding of select client proteins to maintain proteostasis. Through a number of key studies, it has been
shown that Grp94…
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