dc.creator | Pintado Losa, Cristina | es |
dc.creator | Macías Benítez, Sandra | es |
dc.creator | Domínguez Martín, Helena | es |
dc.creator | Castaño Navarro, Angélica | es |
dc.creator | Ruano Caballero, Diego | es |
dc.date.accessioned | 2017-09-20T16:54:17Z | |
dc.date.available | 2017-09-20T16:54:17Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Pintado Losa, C., Macías, S., Domínguez Martín, H., Castaño Navarro, A. y Ruano Caballero, D. (2017). Neuroinflammation alters cellular proteostasis by producing endoplasmic reticulum stress, autophagy activation and disrupting ERAD activation. Scientific Reports, 7 (8100), 1-12. | |
dc.identifier.issn | 2045-2322 | es |
dc.identifier.uri | http://hdl.handle.net/11441/64532 | |
dc.description.abstract | Proteostasis alteration and neuroinflammation are typical features of normal aging. We have previously shown that neuroinflammation alters cellular proteostasis through immunoproteasome induction, leading to a transient decrease of proteasome activity. Here, we further investigated the role of acute lipopolysaccharide (LPS)-induced hippocampal neuroinflammation in cellular proteostasis. In particular, we focused on macroautophagy (hereinafter called autophagy) and endoplasmic reticulum-associated protein degradation (ERAD). We demonstrate that LPS injection induced autophagy activation that was dependent, at least in part, on glycogen synthase kinase (GSK)-3β activity but independent of mammalian target of rapamycin (mTOR) inhibition. Neuroinflammation also produced endoplasmic reticulum (ER) stress leading to canonical unfolded protein response (UPR) activation with a rapid activating transcription factor (ATF) 6α attenuation that resulted in a time-dependent down-regulation of ERAD markers. In this regard, the time-dependent accumulation of unspliced X-box binding protein (XBP) 1, likely because of decreased inositol-requiring enzyme (IRE) 1α-mediated splicing activity, might underlie in vivo ATF6α attenuation. Importantly, lactacystin-induced activation of ERAD was abolished in both the acute neuroinflammation model and in aged rats. Therefore, we provide a cellular pathway through which neuroinflammation might sensitize cells to neurodegeneration under stress situations, being relevant in normal aging and other disorders where neuroinflammation is a characteristic feature | es |
dc.description.sponsorship | Unión Europea PI12/00445 | es |
dc.description.sponsorship | Unión Europea ERDF PI12/00445 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Nature Publishing Group | es |
dc.relation.ispartof | Scientific Reports, 7 (8100), 1-12. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Neuroinflammation alters cellular proteostasis by producing endoplasmic reticulum stress, autophagy activation and disrupting ERAD activation | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.projectID | PI12/00445 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1038/s41598-017-08722-3 | es |
dc.identifier.doi | 10.1038/s41598-017-08722-3 | es |
idus.format.extent | 13 p. | es |
dc.journaltitle | Scientific Reports | es |
dc.publication.volumen | 7 | es |
dc.publication.issue | 8100 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 12 | es |
dc.contributor.funder | European Union (UE) | |