grant
Neurodegenerative reprograming of microglia in Alzheimer’s disease
Organization ADVANCED SCIENCE RESEARCH CENTERLocation NEW YORK, UNITED STATESPosted 15 Dec 2024Deadline 30 Nov 2029
NIHUS FederalResearch GrantFY20262-ketoglutarate2-oxoglutarateAD dementiaAD modelAD pathologyAD patientsAD riskAD risk factorAD therapyAD treatmentAPOE e4APOE-ε4APOEε4AddressAgingAllelesAllelomorphsAlzheimer Type DementiaAlzheimer disease dementiaAlzheimer disease treatmentAlzheimer risk factorAlzheimer sclerosisAlzheimer syndromeAlzheimer treatmentAlzheimer'sAlzheimer's DiseaseAlzheimer's disease modelAlzheimer's disease pathologyAlzheimer's disease patientAlzheimer's disease riskAlzheimer's disease therapyAlzheimer's pathologyAlzheimer's patientAlzheimer's therapyAlzheimers DementiaAmyloidAmyloid SubstanceAmyloidosisAutomobile DrivingBehavior assessmentBiotechBiotechnologyBrainBrain Nervous SystemCausalityCell BodyCellsCellular StressCellular Stress ResponseChromatinCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalCollaborationsCore FacilityCreativenessDarknessDataDevelopmentDiseaseDisorderDisturbance in cognitionEIF-2 alphaEIF-2alphaEIF-2αElementsEncephalonEnzyme GeneEnzymesEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEtiologyEventExposure toFutureGenesGeneticGenetic studyGrantHeterochromatinHeterogeneityHistonesHortega cellHumanImageImmuneImmunesImpaired cognitionIn VitroInitiation FactorsKnowledgeLate Onset Alzheimer DiseaseLate onset ADMT-bound tauMacrophageMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMeasuresMetabolicMetabolic PathwayMiceMice MammalsMicrogliaMitochondriaModelingModern ManMolecularMorphologyMurineMusMφNerve DegenerationNeuron DegenerationNeurosciencesNew YorkOutcomePathologicPathologyPathway interactionsPeptide Initiation FactorsPhagocytesPhagocytic CellPhenotypePhosphorylationPlayPreventionPrimary Senile Degenerative DementiaProcessProductivityProtein PhosphorylationRegulationResearchResponse to stimulus physiologyRiskRisk FactorsRoleScienceSignal PathwayStimulusStressSynapsesSynapticTau forming aggregatesTauopathiesTechniquesTestingTherapeuticTranslation Initiation FactorTranslational Initiation Factorabnormally aggregated tau proteinaggregation in taualpha Subunit Eukaryotic Initiation Factor 2alpha ketoglutaratealzheimer modelalzheimer riskamebocyteamyloid diseaseamyloid pathologyapo E-4apo E4apo epsilon4apoE epsilon 4apoE-4apoE4apolipoprotein E epsilon 4apolipoprotein E-4apolipoprotein E4behavioral assessmentbiological adaptation to stresscausationcell stresschromatin remodelingcofactorcognitive assessmentcognitive dysfunctioncognitive losscognitive testingcreativitydata integrationdemethylationdevelopmentaldisease causationdrivingeffective therapyeffective treatmentepigeneticallyfilamentous tau inclusiongitter cellhistone methylationimagingin vivoinnovateinnovationinnovativeinsightinsoluble aggregatelate onset alzheimerlife spanlifespanmesogliamicroglial cellmicrogliocytemicrotubule associated protein tau aggregationmicrotubule associated protein tau depositmicrotubule bound taumicrotubule-bound taumitochondrialmouse modelmultiomicsmultiple omicsmurine modelneural degenerationneurodegenerationneurodegenerativeneurological degenerationneuronal degenerationneuropathologic tauneuropathological tauneuroprotectionneuroprotectivenew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnon-geneticnongeneticnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapypaired helical filament of taupanomicspathwaypatient living with Alzheimer's diseasepatient suffering from Alzheimer's diseasepatient with Alzheimer'spatient with Alzheimer's diseasepatients with ADperivascular glial cellpreventpreventingprimary degenerative dementiaprogramsprotein aggregateprotein aggregationreaction; crisisrisk factor for developing Alzheimer'srisk factor in Alzheimer'srisk of developing Alzheimer'sself-aggregate tausenile dementia of the Alzheimer typesocial rolestimulus/responsestress responsestress; reactionsynapsetautau PHFtau Proteinstau accumulationtau aggregatetau aggregationtau associated neurodegenerationtau associated neurodegenerative processtau driven neurodegenerationtau factortau fibrillationtau fibrillizationtau filamenttau inclusiontau induced degenerationtau induced neurodegenerationtau mediated neurodegenerationtau neurodegenerative diseasetau neurofibrillary tangletau neuropathologytau oligomertau paired helical filamenttau pathologytau pathophysiologytau polymerizationtau protein accumulationtau protein aggregationtau proteinopathytau related neurodegenerationtau-induced pathologytau-tau interactiontauopathic neurodegenerative disordertauopathytechnological innovationtherapeutic agent developmenttherapeutic developmenttoolα-ketoglutarateα-oxoglutarateαKGτ Proteinsτ aggregation
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ABSTRACT
Genetic studies implicate microglia—the brain's primary innate immune cells—as major determinants for the
risk of Alzheimer's Disease (AD). In murine AD models, microglia can assume phenotypes with protective or
neurodegenerative functions, such as driving aberrant synapse loss. This proposal aims to elucidate molecular
mechanisms that…
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