grant
Metabolic Plasticity and Neuronal Resilience: Unraveling Adaptive Responses to Chronic mtDNA Damage
Organization UNIVERSITY OF CALIFORNIA, SAN DIEGOLocation LA JOLLA, UNITED STATESPosted 1 Mar 2026Deadline 31 Jan 2028
NIHUS FederalResearch GrantFY2026AD dementiaATP SynthesisATP Synthesis PathwayAffectAgingAlzheimer Type DementiaAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's DiseaseAlzheimers DementiaAmmon HornAntimorphic mutationAspartateAutoregulationBindingCell BodyCell RespirationCellsCellular RespirationChronicCitric Acid CycleCornu AmmonisDNA DamageDNA InjuryDNA MaintenanceDNA StabilityDNA mutationDataDefectDegenerative Neurologic DisordersDendritesDisease ProgressionDominant NegativeDominant-Negative MutantDominant-Negative MutationDysfunctionElectron TransportEnergy ExpenditureEnergy MetabolismEnzyme GeneEnzymesEquilibriumFISH TechnicFISH TechniqueFISH analysisFISH assayFluorescence In Situ HybridizationFluorescent in Situ HybridizationFunctional disorderGenetic ChangeGenetic defectGenetic mutationGenomeGlutamatesHealthHippocampusHomeostasisImpairmentIntermediary MetabolismKrebs CycleL-AspartateL-GlutamateLeadLinkMaintenanceMeasuresMediatingMembrane PotentialsMetabolicMetabolic PathwayMetabolic ProcessesMetabolic dysfunctionMetabolic stressMetabolismMicroelectrodesMiniaturized ElectrodesMitochondriaMitochondrial DNAMitochondrial ProteinsModelingMolecularMolecular InteractionMolecular TargetMorphologyMotilityMutateMutationNerve CellsNerve DegenerationNerve UnitNervous System Degenerative DiseasesNeural CellNeural Degenerative DiseasesNeural TransmissionNeural degenerative DisordersNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeuron DegenerationNeuronal DysfunctionNeuronsParalysis AgitansParkinsonParkinson DiseasePathogenicityPathway interactionsPb elementPhysiologicPhysiologicalPhysiological HomeostasisPhysiopathologyPoint MutationPolymerasePrimary ParkinsonismPrimary Senile Degenerative DementiaProductionProteinsProteomicsResting PotentialsRoleShapesStressSynapsesSynapticSynaptic TransmissionSyndromeTCA cycleTechniquesTestingTimeTransmembrane PotentialsTricarboxylic Acid CycleVariantVariationWorkaerobic metabolismaerobic respirationage associatedage associated neurodegenerationage associated neurodegenerative diseaseage associated neurodegenerative disorderage correlatedage dependentage dependent neurodegenerationage dependent neurodegenerative conditionage dependent neurodegenerative diseaseage dependent neurodegenerative disorderage linkedage relatedage related neurodegenerationage specificage-driven neurodegenerative disordersage-related neurodegenerative diseaseage-related neurodegenerative disorderaging associated diseaseaging associated disordersaging associated neurodegenerationaging associated neurodegenerative diseaseaging related diseaseaging related disordersaging related neurodegenerationaging related neurodegenerative diseaseaging related neurodegenerative disorderbalancebalance functionconditional knock-outconditional knockoutdecline in functiondecline in functional statusdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdisease associated with agingdisease of agingdisorder of agingdisorders associated with agingdisorders related to agingelectron transferexcitatory neuronexperimentexperimental researchexperimental studyexperimentsfunctional declinefunctional status declinegenome mutationglutamatergicheavy metal Pbheavy metal leadheteroplasmyhippocampalknock-downknockdownmeetingmeetingsmitochondrialmitochondrial DNA mutationmitochondrial dysfunctionmitochondrial membranemitochondrial metabolismmitochondrial transcription factor AmtDNAmtDNA mutationmtTF1 mitochondrial transcription factor 1mtTF1 transcription factornerve cell deathnerve cell lossnerve cell metabolismneural degenerationneural dysfunctionneurodegenerationneurodegenerativeneurodegenerative illnessneurological degenerationneuron cell deathneuron cell lossneuron cell metabolismneuron deathneuron lossneuron metabolismneuronalneuronal cell deathneuronal cell lossneuronal cell metabolismneuronal deathneuronal degenerationneuronal lossneuronal metabolismneurotoxicoverexpressoverexpressionoxidative metabolismpathophysiologypathwaypolarized cellpreservationpreventpreventingprimary degenerative dementiaprotein expressionresilienceresilientresponsesenile dementia of the Alzheimer typesensorshRNAshort hairpin RNAsmall hairpin RNAsocial rolesynapsesynapse functionsynaptic function
Description preview
Project Summary
Neurons are highly polarized cells with exceptionally high energy demands, met primarily by mitochondrial
oxidative metabolism, which generates ~90% of neuronal ATP. Therefore, mitochondrial dysfunction resulting
from impaired mitochondrial (mt)DNA maintenance has been consistently linked to age-related
neurodegenerative disorders.…
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