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

2020-05-01Artigo científico Acesso aberto
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dc.contributor.authorVicente Miranda, Hugo
dc.contributor.authorChegão, Ana
dc.contributor.authorOliveira, Márcia S.
dc.contributor.authorFernandes Gomes, Bárbara
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorOuteiro, Tiago Fleming
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.pblFederation of American Soc of Exp Biology
dc.date.accessioned2023-05-02T22:08:57Z
dc.date.available2023-05-02T22:08:57Z
dc.date.issued2020-05-01
dc.descriptionFunding: 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).
dc.description.abstractα-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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent11
dc.format.extent1032280
dc.identifier.doi10.1096/fj.201902936R
dc.identifier.issn0892-6638
dc.identifier.otherPURE: 17839137
dc.identifier.otherPURE UUID: a1f9e804-07f6-40e3-a6c2-f27653df66a6
dc.identifier.otherScopus: 85082954892
dc.identifier.otherWOS: 000525285600001
dc.identifier.otherPubMed: 32259355
dc.identifier.urihttp://hdl.handle.net/10362/152336
dc.identifier.urlhttps://www.scopus.com/pages/publications/85082954892
dc.language.isoeng
dc.peerreviewedyes
dc.subjectalpha-synuclein
dc.subjectglycation
dc.subjectHsp27
dc.subjectneurodegeneration
dc.subjectParkinson's disease
dc.subjectBiotechnology
dc.subjectBiochemistry
dc.subjectMolecular Biology
dc.subjectGenetics
dc.titleHsp27 reduces glycation-induced toxicity and aggregation of alpha-synucleinen
dc.typejournal article
degois.publication.firstPage6718
degois.publication.issue5
degois.publication.lastPage6728
degois.publication.titleFaseb Journal
degois.publication.volume34
dspace.entity.typePublication
rcaap.rightsopenAccess

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