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Peripheral mitochondrial function correlates with clinical severity in idiopathic Parkinson’s disease

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dc.creatorMilanese, Chiaraspa
dc.creatorPayan-Gomez, Cesar
dc.creatorGalvani, Martaspa
dc.creatorGonzález, Nicolás Molanospa
dc.creatorTresini, Mariaspa
dc.creatorAbdellah, Soraya Naitspa
dc.creatorvan Roon?Mom, Willeke M. C.spa
dc.creatorFigini, Silviaspa
dc.creatorMarinus, Johanspa
dc.creatorvan Hilten, Jacobus J.spa
dc.creatorMastroberardino, Pier G.spa
dc.date.accessioned2020-05-25T23:57:13Z
dc.date.available2020-05-25T23:57:13Z
dc.date.created2019spa
dc.description.abstractBackground: Parkinson’s disease is an intractable disorder with heterogeneous clinical presentation that may reflect different underlying pathogenic mechanisms. Surrogate indicators of pathogenic processes correlating with clinical measures may assist in better patient stratification. Mitochondrial function, which is impaired in and central to PD pathogenesis, may represent one such surrogate indicator. Methods: Mitochondrial function was assessed by respirometry experiment in fibroblasts derived from idiopathic patients (n = 47) in normal conditions and in experimental settings that do not permit glycolysis and therefore force energy production through mitochondrial function. Respiratory parameters and clinical measures were correlated with bivariate analysis. Machine-learning-based classification and regression trees were used to classify patients on the basis of biochemical and clinical measures. The effects of mitochondrial respiration on ?-synuclein stress were assessed monitoring the protein phosphorylation in permitting versus restrictive glycolysis conditions. Results: Bioenergetic properties in peripheral fibroblasts correlate with clinical measures in idiopathic patients, and the correlation is stronger with predominantly nondopaminergic signs. Bioenergetic analysis under metabolic stress, in which energy is produced solely by mitochondria, shows that patients’ fibroblasts can augment respiration, therefore indicating that mitochondrial defects are reversible. Forcing energy production through mitochondria, however, favors ?-synuclein stress in different cellular experimental systems. Machine-learning-based classification identified different groups of patients in which increasing disease severity parallels higher mitochondrial respiration. Conclusion: The suppression of mitochondrial activity in PD may be an adaptive strategy to cope with concomitant pathogenic factors. Moreover, mitochondrial measures in fibroblasts are potential peripheral biomarkers to follow disease progression. © 2019 The Authors.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1002/mds.27723
dc.identifier.issn08853185
dc.identifier.issn15318257
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22631
dc.language.isoengspa
dc.publisherJohn Wiley and Sons Inc.spa
dc.relation.citationEndPage1202
dc.relation.citationIssueNo. 8
dc.relation.citationStartPage1192
dc.relation.citationTitleMovement Disorders
dc.relation.citationVolumeVol. 34
dc.relation.ispartofMovement Disorders, ISSN:08853185, 15318257, Vol.34, No.8 (2019); pp. 1192-1202spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85071052960&doi=10.1002%2fmds.27723&partnerID=40&md5=bdb9830ff62f52948da04fa6995e56bbspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordAlpha synucleinspa
dc.subject.keywordGalactosespa
dc.subject.keywordGlucosespa
dc.subject.keywordLevodopaspa
dc.subject.keywordRotenonespa
dc.subject.keywordAgedspa
dc.subject.keywordArticlespa
dc.subject.keywordBiochemical analysisspa
dc.subject.keywordBioenergyspa
dc.subject.keywordBivariate analysisspa
dc.subject.keywordCell functionspa
dc.subject.keywordClinical articlespa
dc.subject.keywordClinical featurespa
dc.subject.keywordCorrelation analysisspa
dc.subject.keywordCross-sectional studyspa
dc.subject.keywordDisease severityspa
dc.subject.keywordEnergy yieldspa
dc.subject.keywordFemalespa
dc.subject.keywordGlycolysisspa
dc.subject.keywordHumanspa
dc.subject.keywordIdiopathic diseasespa
dc.subject.keywordIn vitro studyspa
dc.subject.keywordMachine learningspa
dc.subject.keywordMalespa
dc.subject.keywordMetabolic stressspa
dc.subject.keywordMitochondrial respirationspa
dc.subject.keywordMitochondrionspa
dc.subject.keywordOxidative phosphorylationspa
dc.subject.keywordParkinson diseasespa
dc.subject.keywordPathogenesisspa
dc.subject.keywordPriority journalspa
dc.subject.keywordProtein phosphorylationspa
dc.subject.keywordRespirometryspa
dc.subject.keywordAerobic metabolismspa
dc.subject.keywordClinical outcomespa
dc.subject.keywordDisease durationspa
dc.subject.keywordDisease severityspa
dc.subject.keywordFibroblastspa
dc.subject.keywordHuman cellspa
dc.subject.keywordIdiopathic diseasespa
dc.subject.keywordMolecular pathologyspa
dc.subject.keywordOxygen consumptionspa
dc.subject.keywordParkinson diseasespa
dc.subject.keywordSh-sy5y cell linespa
dc.subject.keywordSynucleinopathyspa
dc.subject.keywordUnified parkinson disease rating scalespa
dc.subject.keywordUpregulationspa
dc.subject.keywordClinical phenotypingspa
dc.subject.keywordMitochondriaspa
dc.subject.keywordParkinson’s diseasespa
dc.subject.keyword?-synucleinspa
dc.titlePeripheral mitochondrial function correlates with clinical severity in idiopathic Parkinson’s diseasespa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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