grant
Investigating aberrant vesicular degradation and lipid metabolism in neurodegeneration
Organization UNIV OF MASSACHUSETTS MED SCH WORCESTERLocation WORCESTER, UNITED STATESPosted 15 Aug 2025Deadline 31 Jul 2029
NIHUS FederalResearch GrantFY2025Actin-Binding ProteinActinsAddressAffinityAmyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis Motor Neuron DiseaseAmyotrophic lateral sclerosis and frontotemporal degenerationAmyotrophic lateral sclerosis and frontotemporal dementiaAssayAstrocytesAstrocytusAstrogliaAutophagocytosisBindingBioassayBiological AssayBiophysicsBody TissuesCNS Nervous SystemCausalityCell BodyCellsCellular MatrixCentral Nervous SystemClinicalCompensationComplexCytoskeletal GeneCytoskeletal ProteinsCytoskeletal SystemCytoskeletonDNA mutationDNA-Binding ProteinsDataDefectDegenerative Neurologic DisordersDegradation PathwayDegradative PathwayDiagnosisDiseaseDisease ProgressionDisorderDrug TherapyDysfunctionEnvironmentEtiologyExhibitsFTD dementiaFTD/ALSFTLD/ALSFluorescence SpectroscopyFrontal Temporal DementiaFrontotemporal DementiaFrontotemporal Lobar Degeneration/Amyotrophic lateral sclerosisFunctional disorderGehrig's DiseaseGene AlterationGene MutationGenesGeneticGenetic ChangeGenetic defectGenetic mutationGoalsHereditaryHortega cellImpairmentInheritedInositide PhospholipidsInositol PhosphoglyceridesInositol PhospholipidsInvestigationKI miceKnock-in MouseKnowledgeL-ProlineLaboratoriesLigandsLinkLipidsLou Gehrig DiseaseLysosomesMediatingMembraneMethodsMiceMice MammalsMicrogliaModelingMolecular Dynamics SimulationMolecular InteractionMotor CellMotor NeuronsMurineMusMutationNMR SpectrometerNMR SpectroscopyNerve DegenerationNervous System Degenerative DiseasesNeural Degenerative DiseasesNeural degenerative DisordersNeuraxisNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeuron DegenerationOutcomeOutcome StudyPathogenesisPathologicPathway interactionsPhagocytesPhagocytic CellPhagocytosisPharmacological TreatmentPharmacotherapyPhenotypePhosphatidyl InositolPhosphatidylinositolsPhosphoinositidesPhysiologicPhysiologicalPhysiopathologyPlayPolymersProgressive DiseaseProlineProteinsPtdINS3PPtdInsRNA-Binding ProteinsRecombinantsRelaxationResearchRoleSourceTAR DNA-binding protein 43TDP-43TDP43ThermodynamicThermodynamicsTissuesVariantVariationamebocyteamyotrophic lateral sclerosis with frontotemporal dementiaamyotrophic lateral sclerosis/FTLDamyotrophic lateral sclerosis/frontotemporal dementiaamyotrophic lateral sclerosis/ftdastrocytic gliaautophagybiophysical approachesbiophysical foundationbiophysical methodologybiophysical methodsbiophysical principlesbiophysical sciencesbiophysical techniquescausationcell typedegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdisease causationdrug interventiondrug treatmentexperimentexperimental researchexperimental studyexperimentsfALSfamilial ALSfamilial amyotrophic lateral sclerosisfat metabolismfront temporal dementiafrontal lobe dementiafrontotemporal dementia-amyotrophic lateral sclerosisfrontotemporal lobar degeneration dementiafrontotemporal lobar dementiafrontotemporal lobar dementia amyotrophic lateral sclerosisfrontotemporal lobe degeneration associated with dementiagene defectgenome mutationgitter cellhiPSChuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellsiPSiPSCiPSCsin vivoinduced human pluripotent stem cellsinduced pluripotent cellinduced pluripotent stem cellinducible pluripotent cellinducible pluripotent stem cellinsightintracellular skeletonknockin micelipid metabolismlipidomicsmembrane structuremesogliamicroglial cellmicrogliocytemolecular dynamicsmonomermotoneuronmotor neuron degenerationmouse modelmurine modelmutantmutant alleleneural degenerationneurodegenerationneurodegenerativeneurodegenerative illnessneurological degenerationneuronal degenerationnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetnuclear magnetic resonance spectroscopypathophysiologypathwayperivascular glial cellpharmaceutical interventionpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticsphosphatidylinositol 3-monophosphatephosphatidylinositol 3-phosphatepolymerpolymericpolymerizationprofilin 1profilin Iprotein TDP-43protein TDP43responsesocial rolestructural mutationstructural variantstructural variationvirtual
Description preview
BOSCO/MASSI – ABSTRACT
Profilin-1 (PFN1) is an actin-binding protein that is best known for its role in regulating cytoskeletal dynamics. In
2012, we identified mutations in PFN1 that cause the uniformly lethal neurodegenerative disease amyotrophic
lateral sclerosis (ALS), however, the mechanism underlying PFN1-mediated ALS remains poorly…
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