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
Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice
Cheng X, Tang Y, Vidyadhara D, Li B, Zimmerman M, Pak A, Nareddula S, Edens P, Chandra S, Chubykin A. Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice. IScience 2023, 26: 107842. PMID: 37766983, PMCID: PMC10520332, DOI: 10.1016/j.isci.2023.107842.Peer-Reviewed Original ResearchParkinson's diseasePyramidal cell synapsesVisual cortical functionSilicon probe recordingsPrimary visual cortexShort-term facilitationFamilial Parkinson's diseaseCortical dysfunctionMotor deficitsMotor symptomsCell synapsesCortical functionRepetitive stimulationVisual cortexOptokinetic responseReleasable poolProlonged stimulationLayer 4Visual responsesMiceSynaptic vesiclesEye movementsOrientation selectivityDysfunctionFunction mutationsDopamine 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 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 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 ResearchConceptsParkinson's diseasePD mutationsPresynaptic proteinsSynucleinΑ-synucleinPresynaptic architectureUltrastructural changesAbundant presynaptic proteinPathological functionsPresynaptic cytomatrixImportant orchestratorsProtein phosphorylation changesDiseaseMultiple effectsActive zonePrevious findingsPD mutantsPathogenesisNeurotransmissionSynapse architecturePhosphorylation changesMutationsMice
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
2009
Synucleins
Chandra S. Synucleins. 2009, 833-837. DOI: 10.1016/b978-008045046-9.01354-1.Peer-Reviewed Original Research
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