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(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis

2018Journal article Open access
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dc.contributor.authorMacedo, Diana
dc.contributor.authorJardim, Carolina
dc.contributor.authorFigueira, Inês
dc.contributor.authorAlmeida, A. Filipa
dc.contributor.authorMcDougall, Gordon J.
dc.contributor.authorStewart, Derek
dc.contributor.authorYuste, Jose E.
dc.contributor.authorTomás-Barberán, Francisco A.
dc.contributor.authorTenreiro, Sandra
dc.contributor.authorOuteiro, Tiago
dc.contributor.authorSantos, Cláudia N.
dc.date.accessioned2021-10-27T14:36:10Z
dc.date.available2021-10-27T14:36:10Z
dc.date.issued2018
dc.description© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractParkinson's disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H2O2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia [iNOVA4Health: UID/Multi/04462/2013, SFRH/BD/73429/2010 and IMM/BI/78-2017 to DM, SFRH/BD/86584/2012 to IF, IF/01097/2013 to CNS, SFRH/BPD/35767/2007 and SFRH/BPD/101646/2014 to ST]. BacHBerry FP7 KBBE-2013-7 613793 to CNS, DM and CJ, Marie Curie International Reintegration Grant and an EMBO Installation Grant to TFO. TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSci Rep. 2018 May 3;8(1):6965pt_PT
dc.identifier.doi10.1038/s41598-018-25118-zpt_PT
dc.identifier.eissn2045-2322
dc.identifier.urihttp://hdl.handle.net/10451/50037
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationIMM/BI/78-2017pt_PT
dc.relationIF/01097/2013pt_PT
dc.relationDECIPHERING THE POTENTIAL OF BLACKBERRY POLYPHENOLS FOR PARKINSON DISEASE: DIGESTION, BLOOD BRAIN BARRIER TRANSPOSITION AND NEUROPROTECTIVE EFFECT
dc.relationDECIPHERING THE ROLE OF ALFA-SYNUCLEIN PHOSPHORYLATION IN PARKINSON’S DISEASE
dc.relationDissecting the role of alpha-synuclein phosphorylation in Parkinson’s disease
dc.relation.publisherversionhttps://www.nature.com/srep/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.title(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDECIPHERING THE POTENTIAL OF BLACKBERRY POLYPHENOLS FOR PARKINSON DISEASE: DIGESTION, BLOOD BRAIN BARRIER TRANSPOSITION AND NEUROPROTECTIVE EFFECT
oaire.awardTitleDECIPHERING THE ROLE OF ALFA-SYNUCLEIN PHOSPHORYLATION IN PARKINSON’S DISEASE
oaire.awardTitleDissecting the role of alpha-synuclein phosphorylation in Parkinson’s disease
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04462%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F73429%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F86584%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F35767%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F101646%2F2014/PT
oaire.citation.issue1pt_PT
oaire.citation.titleScientific Reportspt_PT
oaire.citation.volume8pt_PT
oaire.fundingStream5876
oaire.fundingStreamSFRH
person.familyNameMacedo
person.familyNameCarreira Gomes Jardim
person.familyNameNogueira Tenreiro
person.familyNameOuteiro
person.givenNameDiana
person.givenNameCarolina Emanuel
person.givenNameSandra Isabel
person.givenNameTiago
person.identifierhttps://scholar.google.com/citations?user=PWfEE0QAAAAJ&hl=pt-BR&oi=sra
person.identifierA-9289-2013
person.identifier.ciencia-id2115-AAB3-4424
person.identifier.ciencia-id2214-5455-2764
person.identifier.ciencia-idBC14-20AB-8D68
person.identifier.orcid0000-0002-1798-3408
person.identifier.orcid0000-0001-6929-6469
person.identifier.orcid0000-0001-7272-5842
person.identifier.orcid0000-0003-1679-1727
person.identifier.ridI-4391-2014
person.identifier.scopus-author-id54585747300
person.identifier.scopus-author-id6602925840
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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