Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/106750
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dc.contributor.authorAnjo, Sandra I.-
dc.contributor.authorDos Santos, Patrícia Valério-
dc.contributor.authorRosado, Luiza-
dc.contributor.authorBaltazar, Graça-
dc.contributor.authorBaldeiras, Inês-
dc.contributor.authorPires, Diana-
dc.contributor.authorGomes, Andreia-
dc.contributor.authorJanuário, Cristina-
dc.contributor.authorCastelo-Branco, Miguel-
dc.contributor.authorGrãos, Mário-
dc.contributor.authorManadas, Bruno-
dc.date.accessioned2023-04-20T11:12:26Z-
dc.date.available2023-04-20T11:12:26Z-
dc.date.issued2020-
dc.identifier.issn2047-9158pt
dc.identifier.urihttps://hdl.handle.net/10316/106750-
dc.description.abstractBackground: The identification of circulating biomarkers that closely correlate with Parkinson’s Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods: The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results: From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis. Conclusions: In this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.pt
dc.language.isoengpt
dc.publisherSpringer Naturept
dc.relationThis work was financed by the European Regional Development Fund (ERDF) through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, I.P., under projects: POCI-01-0145-FEDER- 029311 (ref.: PTDC/BTM-TEC/29311/2017), PTDC/NEU-NMC/0205/2012, UIDB/ 04539/2020, POCI-01-0145-FEDER-016428 (ref.: SAICTPAC/0010/2015), POCI- 01-0145-FEDER-016795 (ref.: PTDC/NEU-SCC/7051/2014), and POCI-01-0145- FEDER-029516 (PTDC/MED-NEU/29516/2017).pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectMitochondrial-related proteinspt
dc.subjectSWATH-MSpt
dc.subjectParkinson’s diseasept
dc.subjectBiomarker discoverypt
dc.subjectBlood-biomarkerpt
dc.subjectSecretomespt
dc.subjectOxidative stresspt
dc.subject.meshAgedpt
dc.subject.meshAged, 80 and overpt
dc.subject.meshApoptosispt
dc.subject.meshBiomarkerspt
dc.subject.meshCells, Culturedpt
dc.subject.meshCohort Studiespt
dc.subject.meshFemalept
dc.subject.meshHeLa Cellspt
dc.subject.meshHumanspt
dc.subject.meshMalept
dc.subject.meshMiddle Agedpt
dc.subject.meshMitochondrial Proteinspt
dc.subject.meshOxidative Stresspt
dc.subject.meshParkinson Diseasept
dc.subject.meshPilot Projectspt
dc.subject.meshProteomicspt
dc.subject.meshTranslational Research, Biomedicalpt
dc.subject.meshVesicular Transport Proteinspt
dc.titleA different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson's disease potential biomarkerspt
dc.typearticle-
degois.publication.firstPage11pt
degois.publication.issue1pt
degois.publication.titleTranslational Neurodegenerationpt
dc.peerreviewedyespt
dc.identifier.doi10.1186/s40035-020-00188-0pt
degois.publication.volume9pt
dc.date.embargo2020-01-01*
uc.date.periodoEmbargo0pt
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypearticle-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.fulltextCom Texto completo-
item.languageiso639-1en-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCIBIT - Coimbra Institute for Biomedical Imaging and Translational Research-
crisitem.author.orcid0000-0002-8106-7308-
crisitem.author.orcid0000-0001-5402-3978-
crisitem.author.orcid0000-0003-4364-6373-
crisitem.author.orcid0000-0002-2707-1488-
crisitem.author.orcid0000-0002-2087-4042-
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBIT - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
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