2023
Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease
Vidyadhara D, Somayaji M, Wade N, Yücel B, Zhao H, Shashaank N, Ribaudo J, Gupta J, Lam T, Sames D, Greene L, Sulzer D, Chandra S. Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease. Cell Reports 2023, 42: 112231. PMID: 36920906, PMCID: PMC10127800, DOI: 10.1016/j.celrep.2023.112231.Peer-Reviewed Original ResearchConceptsParkinson's diseaseMotor deficitsDopamine transporterPathogenesis of PDNigral dopaminergic lossProgressive motor deficitsΑ-synuclein pathologyEarly-onset Parkinson's diseaseDopamine sequestrationDopaminergic vulnerabilityDopaminergic lossKO micePresynaptic sitesKO brainNeurochemical analysisDorsal striatumKnockout miceCardinal featuresReuptake kineticsL-DOPADiseaseSynaptic autophagyFunction mutationsDeficitsMice
2022
Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function
Gorenberg EL, Tieze S, Yücel B, Zhao HR, Chou V, Wirak GS, Tomita S, Lam TT, Chandra SS. Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function. PLOS Biology 2022, 20: e3001590. PMID: 35358180, PMCID: PMC9004782, DOI: 10.1371/journal.pbio.3001590.Peer-Reviewed Original ResearchConceptsPalmitoyl-protein thioesterase 1Disulfide bond formationNeuronal ceroid lipofuscinosisPosttranslational modificationsRole of PPT1Identification of substratesResin-assisted captureEnzyme palmitoyl-protein thioesterase 1Synaptic adhesion moleculesNeurodegenerative diseasesMature proteinMitochondrial proteinsMolecular dissectionPutative substratesDepalmitoylationKnockout mouse brainFunction mutationsStringent screenMolecular pathwaysSynapse functionDisulfide bondsProteinDevastating neurodegenerative diseaseDisease mechanismsSynaptic function