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
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 mutationsDeficitsMiceα-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
2022
Pharmacological Mechanism of the Non-hallucinogenic 5‑HT2A Agonist Ariadne and Analogs
Cunningham M, Bock H, Serrano I, Bechand B, Vidyadhara D, Bonniwell E, Lankri D, Duggan P, Nazarova A, Cao A, Calkins M, Khirsariya P, Hwu C, Katritch V, Chandra S, McCorvy J, Sames D. Pharmacological Mechanism of the Non-hallucinogenic 5‑HT2A Agonist Ariadne and Analogs. ACS Chemical Neuroscience 2022, 14: 119-135. PMID: 36521179, PMCID: PMC10147382, DOI: 10.1021/acschemneuro.2c00597.Peer-Reviewed Original ResearchConceptsHead-twitch responseParkinson's diseaseHallucinogenic effectsTherapeutic effectTherapeutic potentialClinical therapeutic effectSevere motor deficitsNew drug classesRemarkable therapeutic effectsConsiderable therapeutic potentialComplete remissionRapid remissionMotor deficitsNeurological indicationsTwitch responseClinical resultsReceptor agonistClinical trialsPharmacological mechanismsDrug classesDopamine receptorsMembrane monoamine transporterPreclinical resultsPlasma membrane monoamine transporterGeriatric subjects
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 ResearchMeSH KeywordsAlpha-SynucleinAnimalsBrainFemaleGlucosylceramidaseHEK293 CellsHumansMaleMiceMice, TransgenicMutationParkinson DiseasePsychosineConceptsΑ-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 disordersDiseaseSynucleins Have Multiple Effects on Presynaptic Architecture
Vargas KJ, Schrod N, Davis T, Fernandez-Busnadiego R, Taguchi YV, Laugks U, Lucic V, Chandra SS. Synucleins Have Multiple Effects on Presynaptic Architecture. Cell Reports 2017, 18: 161-173. PMID: 28052246, PMCID: PMC5510332, DOI: 10.1016/j.celrep.2016.12.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansMiceMutationParkinson DiseasePresynaptic TerminalsSynaptic VesiclesSynucleinsConceptsParkinson's diseasePD mutationsPresynaptic proteinsSynucleinΑ-synucleinPresynaptic architectureUltrastructural changesAbundant presynaptic proteinPathological functionsPresynaptic cytomatrixImportant orchestratorsProtein phosphorylation changesDiseaseMultiple effectsActive zonePrevious findingsPD mutantsPathogenesisNeurotransmissionSynapse architecturePhosphorylation changesMutationsMice