2024
Decoding 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
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 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
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
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