Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein

Detalhes bibliográficos
Autor(a) principal: Vicente Miranda, Hugo
Data de Publicação: 2020
Outros Autores: Chegão, Ana, Oliveira, Márcia S., Fernandes Gomes, Bárbara, Enguita, Francisco J., Outeiro, Tiago Fleming
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/152336
Resumo: Funding: This study was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/NEU-OSD/5644/2014 and EXPL/NEU-OSD/0606/2012. Authors were supported by: HVM (FCT, SFRH/BPD/109347/2015); MO (FCT, EXPL/ NEU-OSD/0606/2012); AC (FCT, PD/BD/136863/2018; ProRegeM—PhD program, mechanisms of disease and regenerative medicine); BFG (PTDC/NEU-OSD/5644/2014). TFO is supported an EU Joint Program—Neurodegenerative Disease Research (JPND) project (aSynProtec). The project is supported through the following funding organizations under the aegis of JPND—www.jpnd.edu (BMBF).
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spelling Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synucleinalpha-synucleinglycationHsp27neurodegenerationParkinson's diseaseBiotechnologyBiochemistryMolecular BiologyGeneticsFunding: This study was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/NEU-OSD/5644/2014 and EXPL/NEU-OSD/0606/2012. Authors were supported by: HVM (FCT, SFRH/BPD/109347/2015); MO (FCT, EXPL/ NEU-OSD/0606/2012); AC (FCT, PD/BD/136863/2018; ProRegeM—PhD program, mechanisms of disease and regenerative medicine); BFG (PTDC/NEU-OSD/5644/2014). TFO is supported an EU Joint Program—Neurodegenerative Disease Research (JPND) project (aSynProtec). The project is supported through the following funding organizations under the aegis of JPND—www.jpnd.edu (BMBF).α-synuclein (aSyn) is a major player in Parkinson's disease and a group of other disorders collectively known as synucleinopathies, but the precise molecular mechanisms involved are still unclear. aSyn, as virtually all proteins, undergoes a series of posttranslational modifications during its lifetime, which can affect its biology and pathobiology. We recently showed that glycation of aSyn by methylglyoxal (MGO) potentiates its oligomerization and toxicity, induces dopaminergic neuronal cell loss in mice, and affects motor performance in flies. Small heat-shock proteins (sHsps) are molecular chaperones that facilitate the folding of proteins or target misfolded proteins for clearance. Importantly, sHsps were shown to prevent aSyn aggregation and cytotoxicity. Upon treating cells with increasing amounts of methylglyoxal, we found that the levels of Hsp27 decreased in a dose-dependent manner. Therefore, we hypothesized that restoring the levels of Hsp27 in glycating environments could alleviate the pathogenicity of aSyn. Consistently, we found that Hsp27 reduced MGO-induced aSyn aggregation in cells, leading to the formation of nontoxic aSyn species. Remarkably, increasing the levels of Hsp27 suppressed the deleterious effects induced by MGO. Our findings suggest that in glycating environments, the levels of Hsp27 are important for modulating the glycation-associated cellular pathologies in synucleinopathies.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNVicente Miranda, HugoChegão, AnaOliveira, Márcia S.Fernandes Gomes, BárbaraEnguita, Francisco J.Outeiro, Tiago Fleming2023-05-02T22:08:57Z2020-05-012020-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://hdl.handle.net/10362/152336eng0892-6638PURE: 17839137https://doi.org/10.1096/fj.201902936Rinfo: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:RCAAP2024-03-11T05:34:39Zoai:run.unl.pt:10362/152336Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:54:51.911449Repositório 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 Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
title Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
spellingShingle Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
Vicente Miranda, Hugo
alpha-synuclein
glycation
Hsp27
neurodegeneration
Parkinson's disease
Biotechnology
Biochemistry
Molecular Biology
Genetics
title_short Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
title_full Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
title_fullStr Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
title_full_unstemmed Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
title_sort Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein
author Vicente Miranda, Hugo
author_facet Vicente Miranda, Hugo
Chegão, Ana
Oliveira, Márcia S.
Fernandes Gomes, Bárbara
Enguita, Francisco J.
Outeiro, Tiago Fleming
author_role author
author2 Chegão, Ana
Oliveira, Márcia S.
Fernandes Gomes, Bárbara
Enguita, Francisco J.
Outeiro, Tiago Fleming
author2_role 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 Vicente Miranda, Hugo
Chegão, Ana
Oliveira, Márcia S.
Fernandes Gomes, Bárbara
Enguita, Francisco J.
Outeiro, Tiago Fleming
dc.subject.por.fl_str_mv alpha-synuclein
glycation
Hsp27
neurodegeneration
Parkinson's disease
Biotechnology
Biochemistry
Molecular Biology
Genetics
topic alpha-synuclein
glycation
Hsp27
neurodegeneration
Parkinson's disease
Biotechnology
Biochemistry
Molecular Biology
Genetics
description Funding: This study was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/NEU-OSD/5644/2014 and EXPL/NEU-OSD/0606/2012. Authors were supported by: HVM (FCT, SFRH/BPD/109347/2015); MO (FCT, EXPL/ NEU-OSD/0606/2012); AC (FCT, PD/BD/136863/2018; ProRegeM—PhD program, mechanisms of disease and regenerative medicine); BFG (PTDC/NEU-OSD/5644/2014). TFO is supported an EU Joint Program—Neurodegenerative Disease Research (JPND) project (aSynProtec). The project is supported through the following funding organizations under the aegis of JPND—www.jpnd.edu (BMBF).
publishDate 2020
dc.date.none.fl_str_mv 2020-05-01
2020-05-01T00:00:00Z
2023-05-02T22:08:57Z
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/10362/152336
url http://hdl.handle.net/10362/152336
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0892-6638
PURE: 17839137
https://doi.org/10.1096/fj.201902936R
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11
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
instacron_str RCAAP
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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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