2025
Glucagon-like Peptide-1 receptor agonists for the prevention and treatment of Parkinson’s disease
Lee S, Yin L, Xiao N, Rhee T, Lo H, Wong S, Fox S, Teopiz K, Lam B, Zheng Y, Le G, Mansur R, Rosenblat J, McIntyre R. Glucagon-like Peptide-1 receptor agonists for the prevention and treatment of Parkinson’s disease. CNS Spectrums 2025, 30: e44. PMID: 40485141, DOI: 10.1017/s109285292510031x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGlucagon-Like Peptide-1 Receptor AgonistsHumansNeuroprotective AgentsParkinson DiseaseConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsGLP-1RAsCentral nervous systemReceptor agonistsEvidence of clinically meaningful benefitFood and Drug Administration (FDA)-approved treatmentsTreatment-emergent adverse eventsParkinson's diseaseEffects of GLP-1RAsEmergent adverse eventsClinically meaningful benefitFDA-approved treatmentClinical trial evidenceNo current therapyTreatment of Parkinson's diseasePreclinical evidenceAdverse eventsCurrent therapiesMeaningful benefitClinical evidenceFeatures of PDTherapeutic benefitTrial evidenceInsulin resistanceReduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease
Abulimiti A, Bae H, Ali A, Balakrishnan S, Tsujishita M, Gveric D, Tierney T, Jonas E, Smith P, Gentleman S, Alavian K. Reduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease. Science Advances 2025, 11: eads3051. PMID: 40479058, PMCID: PMC12143374, DOI: 10.1126/sciadv.ads3051.Peer-Reviewed Original ResearchConceptsProximity ligation assayVentral tegmental areaF1Fo-ATP synthaseProximity ligation assay signalsMetabolic efficiencyVentral tegmental area neuronsMitochondrial metabolic efficiencyProtein productionLigation assayMitochondrial activityMetabolic homeostasisIntracellular compartmentsMitochondrial efficiencyDistal neuritesParkinson's diseaseControl postmortem brainsImpaired mitochondrial efficiencySubstantia nigra pars compactaDopaminergic neuron vulnerabilityMesDA neuronsMesencephalic dopaminergicNeuronal vulnerabilityTegmental areaNeuronal subpopulationsIdiopathic Parkinson's diseaseSocioeconomic area deprivation and its relationship with dementia, Parkinson's Disease and all-cause mortality among UK older adults: a multistate modeling approach
Beydoun M, Georgescu M, Weiss J, Noren Hooten N, Beydoun H, Tsai J, Maino Vieytes C, Evans M, Zonderman A. Socioeconomic area deprivation and its relationship with dementia, Parkinson's Disease and all-cause mortality among UK older adults: a multistate modeling approach. Social Science & Medicine 2025, 379: 118137. PMID: 40388863, DOI: 10.1016/j.socscimed.2025.118137.Peer-Reviewed Original ResearchConceptsArea-level deprivationTownsend deprivation indexSocioeconomic statusCardiovascular healthArea-level socioeconomic statusUK older adultsAll-cause mortalityDementia deathsArea deprivationDeprivation indexUK BiobankCox proportional hazardsOlder adultsDementiaParkinson's diseasePD dementiaPotential mediatorsZ-scoreProportional hazardsMultistate modeling approachHealthMortalityMultistate modelWeibull regressionMultistate approachThe bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage
Wang X, Xu P, Bentley-DeSousa A, Hancock-Cerutti W, Cai S, Johnson B, Tonelli F, Shao L, Talaia G, Alessi D, Ferguson S, De Camilli P. The bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage. Nature Cell Biology 2025, 27: 776-789. PMID: 40211074, PMCID: PMC12081312, DOI: 10.1038/s41556-025-01653-6.Peer-Reviewed Original ResearchConceptsDisease genesResponse to lysosomal damageSurface of lysosomesER–lysosome contactsParkinson's disease genesDelivery to lysosomesLipid transport proteinsLysosomal damageVPS13 proteinsLysosomal surfaceDisease proteinsGenetic studiesDamaged lysosomesVPS13CLysosomal stressLipid transportLysosomesInhibited stateMembrane perturbationRab7Lysosomal dysfunctionProteinVps13LipidGenesPolypharmacy and its association with dementia, Parkinson’s disease, and mortality risk in UK adults: a multistate modeling approach
Weiss J, Beydoun M, Georgescu M, Maldonado A, Beydoun H, Noren Hooten N, Tsai J, Song M, Nieva A, Evans M, Zonderman A. Polypharmacy and its association with dementia, Parkinson’s disease, and mortality risk in UK adults: a multistate modeling approach. GeroScience 2025, 47: 4349-4367. PMID: 40080299, PMCID: PMC12181516, DOI: 10.1007/s11357-025-01586-w.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overDementiaFemaleHumansLatent Class AnalysisMaleMiddle AgedParkinson DiseasePolypharmacyRisk FactorsUnited KingdomConceptsHealth transitionOlder adultsCardiovascular healthLatent class analysisUK Biobank participantsRisks associated with polypharmacyHealth statesAssociated with dementiaPopulation-based cohortAssociated with higher riskYears of follow-upMedication combinationsClass analysisBiobank participantsHealth outcomesPolypharmacy statusPolypharmacy prevalenceSocioeconomic statusUK adultsMortality riskDementiaParkinson's diseasePolypharmacyHealthAdverse outcomesMicrostructural patterns in substantia nigra subregions are associated with depression and olfactory impairments in Parkinson’s disease
Mozafar M, Manshadi Z, Molaei Z, Babaei H, Mansouri M, Shahbazi S, Shakeri S, Mirhosseini H, Gulisashvili D, Mayeli M, Initiative P. Microstructural patterns in substantia nigra subregions are associated with depression and olfactory impairments in Parkinson’s disease. Clinical Neurology And Neurosurgery 2025, 251: 108817. PMID: 40080943, DOI: 10.1016/j.clineuro.2025.108817.Peer-Reviewed Original ResearchMeSH KeywordsAgedDepressionDiffusion Tensor ImagingFemaleHumansMaleMiddle AgedOlfaction DisordersParkinson DiseaseSubstantia NigraConceptsDiffusion tensor imagingNon-motor symptomsDopaminergic deficitOlfactory dysfunctionHealthy controlsSubstantia nigraPD patientsParkinson's diseaseDiffusion tensor imaging findingsAssociated with depressionRates of depressionHigher rates of depressionNon-motor testsEvidence of dopaminergic deficitNon-depressed onesOlfactory impairmentAnxiety scoresPrevalence of olfactory dysfunctionDepressionSWEDD groupTensor imagingPPMI databaseDeficitsFA valuesSWEDDLRRK2, lysosome damage, and Parkinson's disease
Bentley-DeSousa A, Clegg D, Ferguson S. LRRK2, lysosome damage, and Parkinson's disease. Current Opinion In Cell Biology 2025, 93: 102482. PMID: 39983584, DOI: 10.1016/j.ceb.2025.102482.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LysosomesParkinson DiseaseConceptsLRRK2 kinase activityKinase activitySubstrate of LRRK2Rab familySmall GTPasesLysosomal biologyDamaged lysosomesEndolysosomal membranesRegulatory mechanismsNormal biologyPathogenesis of Parkinson's diseaseLRRK2Repair mechanismsLysosomal damageLysosomesBiologyGTPaseParkinson's diseaseRabGABARAPActivityCCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models
Leser F, Júnyor F, Pagnoncelli I, Delgado A, Medeiros I, Nóbrega A, Andrade B, de Lima M, da Silva N, Jacob L, Boyé K, Geraldo L, de Souza A, Maron-Gutierrez T, Castro-Faria-Neto H, Follmer C, Braga C, Neves G, Eichmann A, Romão L, Lima F. CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models. Journal Of Neuroinflammation 2025, 22: 31. PMID: 39894839, PMCID: PMC11789347, DOI: 10.1186/s12974-024-03318-x.Peer-Reviewed Original ResearchConceptsMouse model of PDModel of PDMouse modelDopaminergic neuronsNeuron-microglia communicationNeuron-glia communicationParkinson's diseaseCCR7-dependent mannerMicroglial cell activationCCR7 expressionCCL21-CCR7Progressive degenerative diseaseCCR7 receptorMicroglial cell migrationInflammatory profileChemokine CCL21Cell activationCCL21Therapeutic strategiesChemokine inhibitorsTherapeutic implicationsMicroglial activationReceptor pathwayCCR7Behavioral deficitsEvidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional study
Marek K, Russell D, Concha-Marambio L, Choi S, Jennings D, Brumm M, Coffey C, Brown E, Seibyl J, Stern M, Soto C, Siderowf A. Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional study. EBioMedicine 2025, 112: 105567. PMID: 39893720, PMCID: PMC11835612, DOI: 10.1016/j.ebiom.2025.105567.Peer-Reviewed Original ResearchConceptsDementia with Lewy bodiesCross-sectional studyCognitive symptomsParkinson Associated Risk Syndrome StudyPrevention StudyYear follow-upOlder individualsDopamine transporter imagingHigh riskSyndrome studiesParticipantsParkinson's diseaseHyposmic individualsFollow-upSynuclein pathologySymptomsHyposmicsDepartment of DefenseU.S. Department of DefenseIndividualsRiskLewy bodiesClinical parkinsonismMichael J. Fox FoundationDementia
2024
Controversies and insights into PTBP1-related astrocyte-neuron transdifferentiation: neuronal regeneration strategies for Parkinson’s and Alzheimer’s disease
McDowall S, Bagda V, Hodgetts S, Mastaglia F, Li D. Controversies and insights into PTBP1-related astrocyte-neuron transdifferentiation: neuronal regeneration strategies for Parkinson’s and Alzheimer’s disease. Translational Neurodegeneration 2024, 13: 59. PMID: 39627843, PMCID: PMC11613593, DOI: 10.1186/s40035-024-00450-9.Peer-Reviewed Original ResearchConceptsPolypyrimidine tract-binding protein 1Expression of polypyrimidine tract-binding protein 1Stem cell transplantationReprogramming of astrocytesCentral nervous system disordersAlzheimer's diseaseNeurodegenerative disordersNervous system disordersCell transplantationReprogram astrocytesTherapeutic strategiesAnimal modelsSystem disordersDisease outcomeRegenerative therapeuticsNeuronal populationsGlial cellsTherapeutic potentialProtein 1NeuronsAstrocyte heterogeneityDiseaseAstrocytesDisordersPublished studiesTranscranial optogenetic brain modulator for precise bimodal neuromodulation in multiple brain regions
Shin H, Nam M, Lee S, Yang S, Yang E, Jung J, Kim H, Woo J, Cho Y, Yoon Y, Cho I. Transcranial optogenetic brain modulator for precise bimodal neuromodulation in multiple brain regions. Nature Communications 2024, 15: 10423. PMID: 39613730, PMCID: PMC11607408, DOI: 10.1038/s41467-024-54759-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBrainMaleMiceMice, Inbred C57BLOpsinsOptogeneticsParkinson DiseaseConceptsBrain regionsBrain modulesModulation of brain functionTranscranial brain stimulationMultiple brain regionsUpconversion particlesSymptoms of Parkinson's diseaseOptical crosstalkStudy of neural circuitsFood competition testBrain dysfunctionExternal light sourceLight sourcesBrain functionStudy of complex behaviorsSpatial resolutionNeural circuitsBrain disordersDevelopment of treatmentsOptogenetic techniquesBrain stimulationNeural populationsBrainParkinson's diseaseNeuromodulationNeuroimaging Biomarkers in Parkinson’s Disease
Holmes S, Tinaz S. Neuroimaging Biomarkers in Parkinson’s Disease. Advances In Neurobiology 2024, 40: 617-663. PMID: 39562459, DOI: 10.1007/978-3-031-69491-2_21.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersBrainHumansMagnetic Resonance ImagingNeuroimagingParkinson DiseasePositron-Emission TomographyConceptsPublic health burdenNeuroimaging biomarkersTreatment developmentRisk of developing PDParkinson's diseaseHealth burdenDiagnosis of PDMultimodal neuroimaging techniquesIdiopathic Parkinson's diseaseNon-motorDifferential diagnosis of PDNeuroimaging techniquesProdromal phaseDifferential diagnosisSymptomatic treatmentDisease progressionClinical applicationBiomarkersSingle-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 vulnerabilityPhosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits
Kokotos A, Antoniazzi A, Unda S, Ko M, Park D, Eliezer D, Kaplitt M, De Camilli P, Ryan T. Phosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits. Science Advances 2024, 10: eadn6016. PMID: 39167658, PMCID: PMC11338267, DOI: 10.1126/sciadv.adn6016.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsEnergy MetabolismGlycolysisHumansMiceNeuronsParkinson DiseasePhosphoglycerate KinaseConceptsPhosphoglycerate kinase 1Metabolic deficitsExpressions of Phosphoglycerate Kinase 1Dopamine axonsParkinson's diseasePD-associated pathologyViral expressionLoss of functionNeuronal glycolysisSusceptibility lociIn vivoFamilial Parkinson's diseasePD therapeuticsMetabolic lesionsProduction kineticsKinase 1Mitochondrial integrityPhosphoglycerate kinaseBioenergetic deficitsSynaptic dysfunctionGenetic originDeficitsPARK7/DJ-1PhosphoglycerateParkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons
Rafiq N, Fujise K, Rosenfeld M, Xu P, De Camilli P. Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2318943121. PMID: 38635628, PMCID: PMC11047088, DOI: 10.1073/pnas.2318943121.Peer-Reviewed Original ResearchConceptsSynaptojanin 1Endocytic factorsDA neuronsCilia-mediated signalingNerve terminalsIPSC-derived dopaminergic neuronsUbiquitin chainsUbiquitinated proteinsCiliary baseCilia lengthNeurological defectsDopaminergic neuronsProtein dynamicsDomain mutationsAssembly stateIsogenic controlsNeuronsAbnormal accumulationMutationsMiceFocal concentrationParkinsonPI(4UbiquitinEndocytosisCinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial.
Hutchison R, Fraser K, Yang M, Fox T, Hirschhorn E, Njingti E, Scott D, Bedell B, Kistner K, Cedarbaum J, Evans K, Graham D, Martarello L, Mollenhauer B, Lang A, Dam T, Beaver J. Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial. Neurology 2024, 102: e209137. PMID: 38315945, DOI: 10.1212/wnl.0000000000209137.Peer-Reviewed Original ResearchMeSH Keywordsalpha-SynucleinAntibodies, MonoclonalAntiparkinson AgentsBiomarkersDisease ProgressionDopamineDouble-Blind MethodHumansParkinson DiseaseConceptsDisease progressionDopaminergic deficitNeurofilament light chain levelsNigrostriatal dopamine pathwayDopamine transporter SPECTTerminated due to lackStriatal dopaminergic deficitsLight chain levelsClinical disease progressionEvidence of dopaminergic deficitParkinson's diseaseEvaluate disease severityBiomarker measurementsEarly Parkinson's diseaseStriatal binding ratiosDevelopment of therapiesStatistically significant differenceScale total scoreBiomarker resultsDouble-blindPlacebo-controlledUnified Parkinson's Disease Rating Scale total scoreDopamine pathwayClinical trialsPrimary outcomeHerpes Zoster and Risk of Incident Parkinson's Disease in US Veterans: A Matched Cohort Study
Tunnicliffe L, Weil R, Breuer J, Rodriguez‐Barradas M, Smeeth L, Rentsch C, Warren‐Gash C. Herpes Zoster and Risk of Incident Parkinson's Disease in US Veterans: A Matched Cohort Study. Movement Disorders 2024, 39: 438-444. PMID: 38226430, PMCID: PMC10922272, DOI: 10.1002/mds.29701.Peer-Reviewed Original ResearchConceptsUS Department of Veterans AffairsCohort studyRisk of incident PDDepartment of Veterans AffairsCox proportional hazards regressionIncident Parkinson's diseaseAssociated with increased riskHistory of HZMatched cohort studyProportional hazards regressionRisk of PDHerpes zosterIncident PDRisk of incident Parkinson's diseaseVeterans AffairsIncident HZUS veteransPD overallHazards regressionPD riskParkinson's diseaseIncreased riskMatched individualsUS DepartmentAssociated with Parkinson's disease
2023
The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases
Smith R, Capotosti F, Schain M, Ohlsson T, Vokali E, Molette J, Touilloux T, Hliva V, Dimitrakopoulos I, Puschmann A, Jögi J, Svenningsson P, Andréasson M, Sandiego C, Russell D, Miranda-Azpiazu P, Halldin C, Stomrud E, Hall S, Bratteby K, Tampio L’Estrade E, Luthi-Carter R, Pfeifer A, Kosco-Vilbois M, Streffer J, Hansson O. The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases. Nature Communications 2023, 14: 6750. PMID: 37891183, PMCID: PMC10611796, DOI: 10.1038/s41467-023-42305-3.Peer-Reviewed Original ResearchMeSH Keywordsalpha-SynucleinHumansMultiple System AtrophyParkinson DiseasePositron-Emission TomographyConceptsMultiple-system atrophyPositron emission tomographyMultiple-system atrophy patientsDiagnostic work-upMiddle cerebellar peduncleCerebellar white matterParkinson's diseasePositron emission tomography ligandsMultiple system atrophyTarget engagement in vivoTargeted therapyMSA patientsClinical evaluationHealthy controlsIn vitro affinityEmission tomographyPET imagingPET tracersWhite matterSystem atrophyPatientsNeurodegenerative disordersDiseaseA-synucleinRelated disordersMembrane remodeling properties of the Parkinson’s disease protein LRRK2
Wang X, Espadas J, Wu Y, Cai S, Ge J, Shao L, Roux A, De Camilli P. Membrane remodeling properties of the Parkinson’s disease protein LRRK2. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2309698120. PMID: 37844218, PMCID: PMC10614619, DOI: 10.1073/pnas.2309698120.Peer-Reviewed Original ResearchAutophagy markers, cognitive deficits and depressive symptoms in Parkinson’s disease
Li Y, Yang H, Zhao P, Yang J, Yao C, Zhou C, Yang C, Sun X, Li S, Li J. Autophagy markers, cognitive deficits and depressive symptoms in Parkinson’s disease. Journal Of Neural Transmission 2023, 131: 73-81. PMID: 37801108, DOI: 10.1007/s00702-023-02702-w.Peer-Reviewed Original ResearchMeSH KeywordsAutophagyCognitionCognitive DysfunctionDepressionHumansParkinson DiseaseSequestosome-1 ProteinConceptsDepressed PD patientsDepressive symptomsNaming abilityPD patientsHamilton Depression Rating Scale-17Cognitive impairmentNon-depressed PD patientsLC3-II/LC3-IAssociated with delayed recallParkinson's diseaseAssociated with cognitive functionAssociated with MoCA scoresHAMD-17Cognitive deficitsMontreal Cognitive AssessmentDelayed recallCognitive functionCognitive AssessmentGlycolipid parametersAutophagy markersMoCA scoresSymptomsMotor functionImpairmentRecall
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