2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerabilityDecoding transcriptomic signatures of cysteine string protein alpha–mediated synapse maintenance
Wang N, Zhu B, Allnutt M, Grijalva R, Zhao H, Chandra S. Decoding transcriptomic signatures of cysteine string protein alpha–mediated synapse maintenance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320064121. PMID: 38833477, PMCID: PMC11181078, DOI: 10.1073/pnas.2320064121.Peer-Reviewed Original ResearchConceptsSynapse maintenanceTranscriptional changesSynaptogenic adhesion moleculesGene ontology analysisKO miceKO brainMaintenance in vivoCell-cell interactionsGlial cellsSingle-nucleus transcriptomesOntology analysisCspADifferential expressionNeuron-glia interactionsAutophagy-related genesProtein AGenesCell typesNeurodegenerative diseasesInhibitory synapsesLittermate controlsSynaptic pathwaysAdhesion moleculesGlial responseSynapse
2023
α-Synuclein colocalizes with AP180 and affects the size of clathrin lattices
Vargas K, Colosi P, Girardi E, Park J, Harmon L, Chandra S. α-Synuclein colocalizes with AP180 and affects the size of clathrin lattices. Journal Of Biological Chemistry 2023, 299: 105091. PMID: 37516240, PMCID: PMC10470054, DOI: 10.1016/j.jbc.2023.105091.Peer-Reviewed Original ResearchConceptsClathrin punctaClathrin assemblyEndocytic accessory proteinsΑ-synucleinPresynaptic membraneSynaptic vesicle cyclingImmuno-electron microscopyClathrin structuresAccessory proteinsClathrin latticesMembrane curvatureVesicle cyclingCell membranePresynaptic proteinsLipid monolayer systemProteinΓ-synucleinMembranePunctaAssemblyRelocalizesClathrinColocalizesVesicle sizeDeletion
2014
Synucleins Regulate the Kinetics of Synaptic Vesicle Endocytosis
Vargas KJ, Makani S, Davis T, Westphal CH, Castillo PE, Chandra SS. Synucleins Regulate the Kinetics of Synaptic Vesicle Endocytosis. Journal Of Neuroscience 2014, 34: 9364-9376. PMID: 25009269, PMCID: PMC4087213, DOI: 10.1523/jneurosci.4787-13.2014.Peer-Reviewed Original ResearchConceptsSV endocytosisShares high sequence identitySynaptic vesicle endocytosisFamilial PD genesHigh sequence identitySynaptic vesicle traffickingΑ-synucleinVesicle traffickingVesicle endocytosisΓ-synucleinMouse αSequence identityNull culturesBiochemical experimentsPD genesEndocytosisEarly stepsAcidic lipidsPresynaptic proteinsProteinNormal functionPrecise siteSynucleinParkinson's diseaseGenes
2012
Identification of CSPα Clients Reveals a Role in Dynamin 1 Regulation
Zhang YQ, Henderson MX, Colangelo CM, Ginsberg SD, Bruce C, Wu T, Chandra SS. Identification of CSPα Clients Reveals a Role in Dynamin 1 Regulation. Neuron 2012, 74: 136-150. PMID: 22500636, PMCID: PMC3328141, DOI: 10.1016/j.neuron.2012.01.029.Peer-Reviewed Original ResearchConceptsProtein clientsDynamin 1T-SNARE SNAP-25Cysteine string protein αSynaptic vesicle endocytosisSynaptic vesicle fusionChaperone complexClient proteinsVesicle endocytosisSystematic proteomicsSynaptic vesicle numberSuch proteinsCSPαVesicle fusionSNAP-25Synapse maintenanceProtein αVesicle numberProteinNeuronal dysfunctionCochaperonesHsc70ProteomicsEndocytosisHippocampal cultures