2023
Exploring therapeutic strategies for infantile neuronal axonal dystrophy (INAD/PARK14)
Lin G, Tepe B, McGrane G, Tipon R, Croft G, Panwala L, Hope A, Liang A, Zuo Z, Byeon S, Wang L, Pandey A, Bellen H. Exploring therapeutic strategies for infantile neuronal axonal dystrophy (INAD/PARK14). ELife 2023, 12: e82555. PMID: 36645408, PMCID: PMC9889087, DOI: 10.7554/elife.82555.Peer-Reviewed Original ResearchConceptsPatient-derived neural progenitor cellsNeural progenitor cellsPatient-derived neuronsPediatric neurodegenerative disorderRetromer functionMitochondrial morphologyEndolysosomal pathwayMitochondrial defectsProlong lifespanNeurodegenerative phenotypeProgenitor cellsMouse modelRecessive variantsNeurodegenerative disordersGene therapy approachesPathwayInfantile neuroaxonal dystrophyHomologCellsTherapeutic strategiesAzoramidePurkinje cellsFliesPhenotypeMetabolism
2022
Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling
Marcogliese P, Dutta D, Ray S, Dang N, Zuo Z, Wang Y, Lu D, Fazal F, Ravenscroft T, Chung H, Kanca O, Wan J, Douine E, Network U, Pena L, Yamamoto S, Nelson S, Might M, Meyer K, Yeo N, Bellen H. Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling. Science Advances 2022, 8: eabl5613. PMID: 35044823, PMCID: PMC8769555, DOI: 10.1126/sciadv.abl5613.Peer-Reviewed Original ResearchConceptsAxonal lossPatient-derived astrocytesChildhood-onset neurodegenerative disordersNeuronal depletionNeural dysfunctionNeuronal expressionNeurological defectsPharmacological inhibitionNeurodegenerative disordersNeuronal maintenanceNeurological phenotypeWnt antagonistsDownstream signalingIRF2BPLBinding proteinInhibitionWntSignalingWnt transcriptionAstrocytesDysfunctionAntagonistBrain
2018
Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain
Lin G, Lee P, Chen K, Mao D, Tan K, Zuo Z, Lin W, Wang L, Bellen H. Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain. Cell Metabolism 2018, 28: 605-618.e6. PMID: 29909971, DOI: 10.1016/j.cmet.2018.05.019.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-SynucleinAnimalsBrainCell Line, TumorCeramidesDrosophilaDrosophila ProteinsFeedback, PhysiologicalFemaleGroup VI Phospholipases A2Group X Phospholipases A2HeLa CellsHumansLysosomesMaleMembrane FluidityMutationNeuronsNuclear ProteinsParkinson DiseaseRNA-Binding ProteinsSphingolipidsVesicular Transport ProteinsConceptsIPLA2-VIAImpairs synaptic transmissionEarly-onset parkinsonismSynaptic transmissionNeuroaxonal dystrophyParkinson's diseaseNeuronal functionBrain tissueNeurodegenerative disordersΑ-synucleinPLA2G6Ceramide levelsProgressive increaseNeurodegenerationLysosomal stressPositive feedback loopRetromer functionPhospholipid compositionCeramideGlycerol phospholipidsParkinsonismVPS35Desipramine
2017
The Krebs Cycle Enzyme Isocitrate Dehydrogenase 3A Couples Mitochondrial Metabolism to Synaptic Transmission
Ugur B, Bao H, Stawarski M, Duraine LR, Zuo Z, Lin YQ, Neely GG, Macleod GT, Chapman ER, Bellen HJ. The Krebs Cycle Enzyme Isocitrate Dehydrogenase 3A Couples Mitochondrial Metabolism to Synaptic Transmission. Cell Reports 2017, 21: 3794-3806. PMID: 29281828, PMCID: PMC5747319, DOI: 10.1016/j.celrep.2017.12.005.Peer-Reviewed Original ResearchConceptsSynaptic vesiclesKrebs cycle enzymeRole of metabolitesC2 domainPlasma membraneMitochondrial metabolismSynaptic transmissionMetabolic regulationCycle enzymesSynaptic roleAlpha-ketoglutarateSyt1ΑKGNeurodegenerative disordersDependent processesRegulationMetabolitesIDH3ASynaptotagmin1Multiple levelsFliesRoleFusionVesiclesATP