Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles

Detalhes bibliográficos
Autor(a) principal: Pinho, Raquel
Data de Publicação: 2016
Outros Autores: Guedes, Leonor C, Soreq, Lilach, Lobo, Patricia P, Mestre, Tiago, Coelho, Miguel, Rosa, Mario M, Goncalves, Nilza, Wales, Pauline, Mendes, Tiago, Gerhardt, Ellen, Fahlbusch, Christiane, Bonifati, Vincenzo, Bonin, Michael, Miltenberger-Miltenyi, Gabriel, Borovecki, Fran, Soreq, Hermona, Ferreira, Joaquim J, Outeiro, Tiago F
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/26640
Resumo: This project was supported by Fundacao para a Ciencia e Tecnologia (FCT grant PIC/IC/82760/2007). RP is supported by a PhD fellowship from FCT (SFRH/BD/80884/2011). TFO was supported by an EMBO Installation Grant, and is currently supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain, and by a Grant from Parkinson Fonds, Germany. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-20013) under grant agreement No. 241791 European Project on Mendelian Forms of PD (MEFOPA). LS is funded by a Marie Curie Intra-European Fellowship (IEF) within the European Union's Seventh Framework Programme (PRANA-GPF-330430). VB is supported by the Stichting ParkinsonFonds (The Netherlands).
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spelling Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression ProfilesThis project was supported by Fundacao para a Ciencia e Tecnologia (FCT grant PIC/IC/82760/2007). RP is supported by a PhD fellowship from FCT (SFRH/BD/80884/2011). TFO was supported by an EMBO Installation Grant, and is currently supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain, and by a Grant from Parkinson Fonds, Germany. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-20013) under grant agreement No. 241791 European Project on Mendelian Forms of PD (MEFOPA). LS is funded by a Marie Curie Intra-European Fellowship (IEF) within the European Union's Seventh Framework Programme (PRANA-GPF-330430). VB is supported by the Stichting ParkinsonFonds (The Netherlands).The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson's disease (PD) progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified textgreater200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression analysis in aiding patient stratification and therapeutic intervention.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNPinho, RaquelGuedes, Leonor CSoreq, LilachLobo, Patricia PMestre, TiagoCoelho, MiguelRosa, Mario MGoncalves, NilzaWales, PaulineMendes, TiagoGerhardt, EllenFahlbusch, ChristianeBonifati, VincenzoBonin, MichaelMiltenberger-Miltenyi, GabrielBorovecki, FranSoreq, HermonaFerreira, Joaquim JOuteiro, Tiago F2017-12-11T23:27:54Z2016-06-202016-06-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/26640eng1932-6203PURE: 2355667https://doi.org/10.1371/journal.pone.0157852info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:14:01Zoai:run.unl.pt:10362/26640Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:28:31.743731Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
title Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
spellingShingle Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
Pinho, Raquel
title_short Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
title_full Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
title_fullStr Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
title_full_unstemmed Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
title_sort Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles
author Pinho, Raquel
author_facet Pinho, Raquel
Guedes, Leonor C
Soreq, Lilach
Lobo, Patricia P
Mestre, Tiago
Coelho, Miguel
Rosa, Mario M
Goncalves, Nilza
Wales, Pauline
Mendes, Tiago
Gerhardt, Ellen
Fahlbusch, Christiane
Bonifati, Vincenzo
Bonin, Michael
Miltenberger-Miltenyi, Gabriel
Borovecki, Fran
Soreq, Hermona
Ferreira, Joaquim J
Outeiro, Tiago F
author_role author
author2 Guedes, Leonor C
Soreq, Lilach
Lobo, Patricia P
Mestre, Tiago
Coelho, Miguel
Rosa, Mario M
Goncalves, Nilza
Wales, Pauline
Mendes, Tiago
Gerhardt, Ellen
Fahlbusch, Christiane
Bonifati, Vincenzo
Bonin, Michael
Miltenberger-Miltenyi, Gabriel
Borovecki, Fran
Soreq, Hermona
Ferreira, Joaquim J
Outeiro, Tiago F
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Pinho, Raquel
Guedes, Leonor C
Soreq, Lilach
Lobo, Patricia P
Mestre, Tiago
Coelho, Miguel
Rosa, Mario M
Goncalves, Nilza
Wales, Pauline
Mendes, Tiago
Gerhardt, Ellen
Fahlbusch, Christiane
Bonifati, Vincenzo
Bonin, Michael
Miltenberger-Miltenyi, Gabriel
Borovecki, Fran
Soreq, Hermona
Ferreira, Joaquim J
Outeiro, Tiago F
description This project was supported by Fundacao para a Ciencia e Tecnologia (FCT grant PIC/IC/82760/2007). RP is supported by a PhD fellowship from FCT (SFRH/BD/80884/2011). TFO was supported by an EMBO Installation Grant, and is currently supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain, and by a Grant from Parkinson Fonds, Germany. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-20013) under grant agreement No. 241791 European Project on Mendelian Forms of PD (MEFOPA). LS is funded by a Marie Curie Intra-European Fellowship (IEF) within the European Union's Seventh Framework Programme (PRANA-GPF-330430). VB is supported by the Stichting ParkinsonFonds (The Netherlands).
publishDate 2016
dc.date.none.fl_str_mv 2016-06-20
2016-06-20T00:00:00Z
2017-12-11T23:27:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/26640
url http://hdl.handle.net/10362/26640
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
PURE: 2355667
https://doi.org/10.1371/journal.pone.0157852
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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