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 vulnerability
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 sizeDeletionα-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease
Martin-Lopez E, Vidyadhara D, Liberia T, Meller S, Harmon L, Hsu R, Spence N, Brennan B, Han K, Yücel B, Chandra S, Greer C. α-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease. Journal Of Neuroscience 2023, 43: 1051-1071. PMID: 36596700, PMCID: PMC9908323, DOI: 10.1523/jneurosci.1526-22.2022.Peer-Reviewed Original ResearchConceptsΑ-syn tg miceΑ-Syn pathologyOlfactory bulb neurogenesisProjection neuronsParkinson's diseaseOlfactory dysfunctionMutant α-synucleinOlfactory deficitsOlfactory pathwaySyn pathologyBehavioral deficitsMouse modelΑ-synucleinOB granule cellsΑ-synuclein pathologyOlfactory systemMonths of ageReduced neurogenesisFunctional deficitsPeriglomerular cellsMotor progressionPathologic changesMultiple symptomsSynaptic terminalsGranule cells
2017
Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease
Taguchi YV, Liu J, Ruan J, Pacheco J, Zhang X, Abbasi J, Keutzer J, Mistry PK, Chandra SS. Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease. Journal Of Neuroscience 2017, 37: 9617-9631. PMID: 28847804, PMCID: PMC5628407, DOI: 10.1523/jneurosci.1525-17.2017.Peer-Reviewed Original ResearchConceptsΑ-synuclein pathologyParkinson's diseaseCommon genetic risk factorGenetic risk factorsGaucher diseaseRisk factorsPD pathologyOligomeric α-synuclein speciesPD mouse brainPathological aggregationΑ-synuclein speciesHuman cellsAttractive therapeutic targetΑ-synuclein aggregationPrevalent neurodegenerative disorderGD patientsFunction mechanismPD riskMouse linesMutantsTherapeutic targetMutationsMouse brainNeurodegenerative disordersDisease
2005
α-Synuclein Cooperates with CSPα in Preventing Neurodegeneration
Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC. α-Synuclein Cooperates with CSPα in Preventing Neurodegeneration. Cell 2005, 123: 383-396. PMID: 16269331, DOI: 10.1016/j.cell.2005.09.028.Peer-Reviewed Original ResearchConceptsAbundant synaptic vesicle proteinsEndogenous synucleinNeuronal survivalNerve terminalsParkinson's diseaseProgressive neurodegenerationSynaptic vesicle proteinsAlpha-synucleinDownstream mechanismsNeurodegenerationVivo activitySNARE complex assemblyCSPalphaTransgenic expressionDiseaseMicePhysiological roleCochaperone functionVesicle proteinsSNARE proteinsComplex assemblyInjuryDeletionSynuclein