Publicação
(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
| Resumo: | Parkinson'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. |
|---|---|
| Autores principais: | Macedo, Diana |
| Outros Autores: | Jardim, Carolina; Figueira, Inês; Almeida, A. Filipa; McDougall, Gordon J.; Stewart, Derek; Yuste, Jose E.; Tomás-Barberán, Francisco A.; Tenreiro, Sandra; Outeiro, Tiago; Santos, Cláudia N. |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1869345937972789248 |
|---|---|
| author | Macedo, Diana |
| author2 | Jardim, Carolina Figueira, Inês Almeida, A. Filipa McDougall, Gordon J. Stewart, Derek Yuste, Jose E. Tomás-Barberán, Francisco A. Tenreiro, Sandra Outeiro, Tiago Santos, Cláudia N. |
| author2_role | author author author author author author author author author author |
| author_facet | Macedo, Diana Jardim, Carolina Figueira, Inês Almeida, A. Filipa McDougall, Gordon J. Stewart, Derek Yuste, Jose E. Tomás-Barberán, Francisco A. Tenreiro, Sandra Outeiro, Tiago Santos, Cláudia N. |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Macedo, Diana\",\"Person.identifier.orcid\":\"0000-0002-1798-3408\"},{\"Person.name\":\"Jardim, Carolina\",\"Person.identifier.orcid\":\"0000-0001-6929-6469\"},{\"Person.name\":\"Figueira, Inês\"},{\"Person.name\":\"Almeida, A. Filipa\"},{\"Person.name\":\"McDougall, Gordon J.\"},{\"Person.name\":\"Stewart, Derek\"},{\"Person.name\":\"Yuste, Jose E.\"},{\"Person.name\":\"Tomás-Barberán, Francisco A.\"},{\"Person.name\":\"Tenreiro, Sandra\",\"Person.identifier.orcid\":\"0000-0001-7272-5842\"},{\"Person.name\":\"Outeiro, Tiago\",\"Person.identifier.orcid\":\"0000-0003-1679-1727\"},{\"Person.name\":\"Santos, Cláudia N.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Macedo, Diana Jardim, Carolina Figueira, Inês Almeida, A. Filipa McDougall, Gordon J. Stewart, Derek Yuste, Jose E. Tomás-Barberán, Francisco A. Tenreiro, Sandra Outeiro, Tiago Santos, Cláudia N. |
| datacite.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2021-10-27T14:36:10Z |
| datacite.date.embargoed.fl_str_mv | 2021-10-27T14:36:10Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.titles.title.fl_str_mv | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Macedo, Diana Jardim, Carolina Figueira, Inês Almeida, A. Filipa McDougall, Gordon J. Stewart, Derek Yuste, Jose E. Tomás-Barberán, Francisco A. Tenreiro, Sandra Outeiro, Tiago Santos, Cláudia N. |
| dc.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2021-10-27T14:36:10Z |
| dc.date.embargoed.fl_str_mv | 2021-10-27T14:36:10Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/50037 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Springer Nature |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.title.fl_str_mv | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Parkinson'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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
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| funding.funder.alternateName_str_mv | FCT FCT FCT |
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| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.identifier_str_mv | SFRH/BD/86584/2012 SFRH/BPD/35767/2007 SFRH/BPD/101646/2014 |
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| identifier.url.fl_str_mv | http://hdl.handle.net/10451/50037 |
| inst_facet_str | urn:organizationAcronym:ul{{{_:::_}}}Universidade de Lisboa |
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| institution | Universidade de Lisboa |
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| language | eng |
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| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/50037 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Macedo, Diana Macedo, Diana http://orcid.org/0000-0002-1798-3408 0000-0002-1798-3408 Jardim, Carolina Jardim, Carolina https://www.ciencia-id.pt/2115-AAB3-4424 2115-AAB3-4424 http://orcid.org/0000-0001-6929-6469 0000-0001-6929-6469 Figueira, Inês Almeida, A. Filipa McDougall, Gordon J. Stewart, Derek Yuste, Jose E. Tomás-Barberán, Francisco A. Tenreiro, Sandra Tenreiro, Sandra https://www.ciencia-id.pt/2214-5455-2764 2214-5455-2764 http://orcid.org/0000-0001-7272-5842 0000-0001-7272-5842 Outeiro, Tiago Outeiro, Tiago https://www.ciencia-id.pt/BC14-20AB-8D68 BC14-20AB-8D68 http://orcid.org/0000-0003-1679-1727 0000-0003-1679-1727 Santos, Cláudia N. |
| publishDate | 2018 |
| publisher.none.fl_str_mv | Springer Nature |
| repo_facet_str | urn:repositoryAcronym:ul{{{_:::_}}}Repositório da Universidade de Lisboa |
| reponame_str | Repositório da Universidade de Lisboa |
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| spelling | engSpringer Naturept_PTParkinson'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.application/pdfpt_PT(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasisPersonalMacedo, DianaDSpacehttp://dspace.org/items/e08ee571-c498-4450-a5f6-8b76cdbe537dDSpacehttp://dspace.org/items/e08ee571-c498-4450-a5f6-8b76cdbe537dMacedoDianaORCIDhttp://orcid.org0000-0002-1798-3408Researcher IDhttps://www.researcherid.comI-4391-2014Scopus Author IDhttps://www.scopus.com54585747300PersonalJardim, CarolinaDSpacehttp://dspace.org/items/62e8c1d8-8ec3-423c-be3a-df179c91d85fDSpacehttp://dspace.org/items/62e8c1d8-8ec3-423c-be3a-df179c91d85fCarreira Gomes JardimCarolina EmanuelCiência IDhttps://www.ciencia-id.pt2115-AAB3-4424ORCIDhttp://orcid.org0000-0001-6929-6469Figueira, InêsAlmeida, A. FilipaMcDougall, Gordon J.Stewart, DerekYuste, Jose E.Tomás-Barberán, Francisco A.PersonalTenreiro, SandraDSpacehttp://dspace.org/items/b4c00f6c-f883-43e6-9a54-0d2a3e600ae8DSpacehttp://dspace.org/items/b4c00f6c-f883-43e6-9a54-0d2a3e600ae8Nogueira TenreiroSandra IsabelCiência IDhttps://www.ciencia-id.pt2214-5455-2764ORCIDhttp://orcid.org0000-0001-7272-5842Scopus Author IDhttps://www.scopus.com6602925840PersonalOuteiro, TiagoDSpacehttp://dspace.org/items/af7b2e31-d9da-4e83-a8f1-702910f80a40DSpacehttp://dspace.org/items/af7b2e31-d9da-4e83-a8f1-702910f80a40OuteiroTiagoCiência IDhttps://www.ciencia-id.ptBC14-20AB-8D68ORCIDhttp://orcid.org0000-0003-1679-1727Santos, Cláudia N.HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@ulisboa.ptrepositorio@ulisboa.ptDOIIsPartOf10.1038/s41598-018-25118-z2021-10-27T14:36:10Z20182018-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/50037http://purl.org/coar/access_right/c_abf2open access3411100 bytesFundação para a Ciência e a TecnologiaDECIPHERING THE POTENTIAL OF BLACKBERRY POLYPHENOLS FOR PARKINSON DISEASE: DIGESTION, BLOOD BRAIN BARRIER TRANSPOSITION AND NEUROPROTECTIVE EFFECTinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F86584%2F2012/PTSFRH/BD/86584/2012Crossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaDECIPHERING THE ROLE OF ALFA-SYNUCLEIN PHOSPHORYLATION IN PARKINSON’S DISEASEinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F35767%2F2007/PTSFRH/BPD/35767/2007Crossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaDissecting the role of alpha-synuclein phosphorylation in Parkinson’s diseaseinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F101646%2F2014/PTSFRH/BPD/101646/2014Crossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal article2018http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/faf59d87-d8d9-419f-8461-8df076232789/downloadScientific Reports81 |
| spellingShingle | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis Macedo, Diana |
| status | SINGLETON |
| title | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| title_full | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| title_fullStr | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| title_full_unstemmed | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| title_short | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| title_sort | (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis |
| url | http://hdl.handle.net/10451/50037 |
| visible | 1 |
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