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dc.contributor.authorIlieva, Ekaterina V.
dc.contributor.authorNaudí i Farré, Alba
dc.contributor.authorKichev, Anton Vladimirov
dc.contributor.authorFerrer, Isidre
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorPortero Otín, Manuel
dc.date.accessioned2016-11-28T11:45:54Z
dc.date.issued2010
dc.identifier.issn0891-5849
dc.identifier.urihttp://hdl.handle.net/10459.1/58674
dc.description.abstractBoth oxidative and endoplasmic reticulum (ER) stress is associated with multiple neurodegenerative, age-related diseases. The rare disorder Pick disease (PiD) shares some pathological hallmarks of other neurodegenerative diseases that may be related to oxidative stress. Importantly, activation of an ER stress response, which is also involved in aging, has not yet been investigated in PiD. In this study, we assessed the implication of ER stress associated with oxidative stress in PiD as a potential mechanism involved in its pathogenesis. Samples from morphologically affected frontal cortex and apparently pathologically preserved occipital cortex showed region-dependent increases in different protein oxidative damage pathways. The oxidative modifications targeted antioxidant enzymes, proteases, heat shock proteins, and synaptic proteins. These effects were associated with compromised proteasomal function and ER stress in frontal cortex samples. In addition, we observed a depletion in ER chaperones (glucose-regulated proteins Grp78/BiP and glucose-regulated protein 94) and differences in tissue content and distribution of nuclear factor-erythroid 2 p45-related respiratory 2, required for cell survival during the unfolded protein response. These results demonstrate increased region-specific protein oxidative damage in PiD, with proteasomal alteration and dysfunctional ER stress response. We suggest this was caused by complete and specific depletion of Grp78/BiP, contributing to the pathophysiology of this neurodegenerative disease.ca_ES
dc.description.sponsorshipWe are fully indebted to the tissue donors and their families. This work was supported by I+D grants from the Spanish Ministry of Education and Science (AGL2006-12433, BFU2009-06427-E/BFI, BFU2009-11879/BFI), the Generalitat of Catalunya (2009 SGR735), the Spanish Ministry of Health (FIS 04-0355, 04-0184, 05-2214, 05-1570, 08-1843,RD06/0013/0012), and “La Caixa” Foundation to R.P. and M.P.O. E.I. is a predoctoral Fellow from the Generalitat. This work was also supported by the European Commission under the VI Framework Programme (BrainNet Europe II, LSHM-CT- 2004-503039) and by the COST B-35 action.ca_ES
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relationMIECI/PN2004-2007/AGL2006-12433
dc.relationMICINN/PN2008-2011/BFU2009-06427-E/BFI
dc.relationMICINN/PN2008-2011/BFU2009-11879/BFI
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.freeradbiomed.2010.02.006ca_ES
dc.relation.ispartofFree Radical Biology and Medicine, 2010, vol. 48, núm. 10, p. 1302-1310ca_ES
dc.rights(c) Elsevier Inc, 2010ca_ES
dc.subjectFree radicalsca_ES
dc.subjectChaperoneca_ES
dc.subjectProtein oxidationca_ES
dc.subjectMitochondriaca_ES
dc.titleDepletion of oxidative and endoplasmic reticulum stress regulators in Pick diseaseca_ES
dc.typearticleca_ES
dc.identifier.idgrec015600
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2010.02.006
dc.date.embargoEndDate10000-01-01


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