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 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
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