grant
Role of oligomeric TDP-43 aggregate intermediates in ALS and frontotemporal dementia
Organization SAINT LOUIS UNIVERSITYLocation SAINT LOUIS, UNITED STATESPosted 1 Feb 2020Deadline 31 Jan 2027
NIHUS FederalResearch GrantFY2024AD dementiaALS patientsAccelerationAffectAlzheimer Type DementiaAlzheimer beta-ProteinAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's Amyloid beta-ProteinAlzheimer's DiseaseAlzheimer's amyloidAlzheimer's disease patientAlzheimer's patientAlzheimers DementiaAmyloidAmyloid Alzheimer's Dementia Amyloid ProteinAmyloid Beta-PeptideAmyloid Protein A4Amyloid SubstanceAmyloid beta-ProteinAmyloid βAmyloid β-PeptideAmyloid β-ProteinAmyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis Motor Neuron DiseaseAmyotrophic Lateral Sclerosis patientsAmyotrophic lateral sclerosis and frontotemporal degenerationAmyotrophic lateral sclerosis and frontotemporal dementiaAntibodiesAntigenic DeterminantsAβBinding DeterminantsBody TissuesBrainBrain Nervous SystemCell BodyCell modelCellsCellular modelCharacteristicsCollaborationsComplexCore AssemblyCytoplasmDNA-Binding ProteinsDegenerative Neurologic DisordersDiseaseDisease MarkerDisease ProgressionDisorderEarly DiagnosisElectrophoresisElectrophoretic FractionationEncephalonEpitopesFTD/ALSFTLD/ALSFrontal Temporal DementiaFrontotemporal DementiaFrontotemporal Lobar Degeneration/Amyotrophic lateral sclerosisFutureGehrig's DiseaseGenetic AlterationGenetic ChangeGenetic defectGenotoxinsGoalsGrantHumanIn VitroInjectionsIsoformsLesionLinkLou Gehrig DiseaseMT-bound tauMediatingMethodsMiceMice MammalsModelingModern ManMolecularMurineMusMutagensMutationNAC precursorNerve DegenerationNervous System Degenerative DiseasesNervous System DiseasesNervous System DisorderNeural Degenerative DiseasesNeural degenerative DisordersNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeurologic DisordersNeurological DisordersNeuron DegenerationNon-Polyadenylated RNAPARK1 proteinPARK4 proteinParalysis AgitansParkinsonParkinson DiseasePathogenesisPathologicPathologyPatientsPrimary ParkinsonismPrimary Senile Degenerative DementiaProcessProtein CleavageProtein IsoformsProtein RegionProteinsProteolysisPutative RNA-Binding RegionRNARNA Binding DomainRNA Gene ProductsRNA Recognition MotifRNA-Binding ProteinsRNP DomainRNP MotifRNP-1 SignatureReagentRibonucleic AcidRoleSNCASNCA proteinSourceTAR DNA-binding protein 43TDP-43TDP-43 aggregateTDP-43 aggregationTDP43TDP43 aggregateTDP43 aggregationTestingTherapeuticTimeTissuesUniversitiesVariantVariationWashingtonWorka beta peptidea-syna-synucleinaberrant protein foldingabetaabnormal protein foldingalpha synucleinalpha synuclein genealphaSP22amyloid betaamyloid-b proteinamyotrophic lateral sclerosis with frontotemporal dementiaamyotrophic lateral sclerosis/FTLDamyotrophic lateral sclerosis/frontotemporal dementiaamyotrophic lateral sclerosis/ftdasynbeta amyloid fibrilbeta-synucleincartilage link proteincombatdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdetection methoddetection proceduredetection techniquediagnostic approachdiagnostic biomarkerdiagnostic markerdiagnostic strategydisease modeldisorder modelearly detectionfront temporal dementiafrontal lobe dementiafrontotemporal dementia-amyotrophic lateral sclerosisfrontotemporal lobar dementiafrontotemporal lobar dementia amyotrophic lateral sclerosisfrontotemporal lobe degeneration associated with dementiagain of functiongenome mutationgenotoxic agenthnRNP A1in vivoin vivo Modelinsightinsoluble aggregatelink proteinmicrotubule bound taumicrotubule-bound tauneural degenerationneurodegenerationneurodegenerativeneurodegenerative illnessneurological degenerationneurological diseaseneuron toxicityneuronal degenerationneuronal toxicityneurotoxicitynon A-beta component of AD amyloidnon A4 component of amyloid precursorpathologic protein foldingpatient living with Alzheimer's diseasepatient suffering from Alzheimer's diseasepatient with Alzheimer'spatient with Alzheimer's diseasephosphoneuroprotein 14preventpreventingprimary degenerative dementiaprotein TDP-43protein TDP43protein aggregateprotein aggregationprotein misfoldingprotein purificationproteotoxicproteotoxicityrecruitsenile dementia of the Alzheimer typesocial rolesoluble amyloid precursor proteinstress granuletautau Proteinstau factortherapeutically effectivetooltool developmentα synuclein geneα-synα-synucleinτ Proteins
Description preview
The goal of this grant is to elucidate key mechanisms of TDP-43 aggregation by uncovering how this process
leads to pathology and neurotoxicity. TDP-43 aggregation is the pathological hallmark of amyotrophic lateral
sclerosis (ALS) and half of frontotemporal dementia (FTD) cases. In addition, TDP-43 lesions are a secondary
pathology in…
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