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dc.creatorLachén Montes, Mercedeses_ES
dc.creatorGonzález Morales, Andreaes_ES
dc.creatorZelaya, María Victoriaes_ES
dc.creatorPérez Valderrama, Estelaes_ES
dc.creatorAusín, Karinaes_ES
dc.creatorFerrer, Isidroes_ES
dc.creatorFernández Irigoyen, Joaquínes_ES
dc.creatorSantamaría, Enriquees_ES
dc.date.accessioned2018-09-19T09:37:47Z
dc.date.available2018-09-19T09:37:47Z
dc.date.issued2017
dc.identifier.issn2045-2322 (Electronic)
dc.identifier.urihttps://hdl.handle.net/2454/30733
dc.description.abstractOlfactory dysfunction is among the earliest features of Alzheimer’s disease (AD). Although neuropathological abnormalities have been detected in the olfactory bulb (OB), little is known about its dynamic biology. Here, OB- proteome analysis showed a stage-dependent synaptic proteostasis impairment during AD evolution. In addition to progressive modulation of tau and amyloid precursor protein (APP) interactomes, network-driven proteomics revealed an early disruption of upstream and downstream p38 MAPK pathway and a subsequent impairment of Phosphoinositide-dependent protein kinase 1 (PDK1)/Protein kinase C (PKC) signaling axis in the OB from AD subjects. Moreover, a mitochondrial imbalance was evidenced by a depletion of Prohibitin-2 (Phb2) levels and a specific decrease in the phosphorylated isoforms of Phb1 in intermediate and advanced AD stages. Interestingly, olfactory Phb subunits were also deregulated across different types of dementia. Phb2 showed a specific up-regulation in mixed dementia, while Phb1 isoforms were down-regulated in frontotemporal lobar degeneration (FTLD). However, no differences were observed in the olfactory expression of Phb subunits in progressive supranuclear palsy (PSP). To sum up, our data reflect, in part, the missing links in the biochemical understanding of olfactory dysfunction in AD, unveiling Phb complex as a differential driver of neurodegeneration at olfactory level.en
dc.description.sponsorshipThis work was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (Ref. SAF2014-59340-R), Department of Economic Development from Government of Navarra (Ref. PC025), and Obra Social la Caixa to ES. AGM and KA are supported by PEJ-2014-A-61949 and PEJ-2014-A-72151 (MINECO). EPV is supported by PTA-2013/8711/I (MINECO). MLM is supported by a predoctoral fellowship from the Public University of Navarra (UPNA). The Proteomics Unit of Navarrabiomed is a member of Proteored, PRB2-ISCIII, and is supported by grant PT13/0001, of the PE I + D + I 2013-2016 funded by ISCIII and FEDER.en
dc.format.extent15 p.
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/zipen
dc.language.isoengen
dc.publisherSpringer Natureen
dc.relation.ispartofScientific Reports, 7: 9115en
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHealthen
dc.subjectRadio planningen
dc.titleOlfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer's disease progressionen
dc.typeinfo:eu-repo/semantics/articleen
dc.typeArtículo / Artikuluaes
dc.contributor.departmentUniversidad Pública de Navarra. Departamento de Ciencias de la Saludes_ES
dc.contributor.departmentNafarroako Unibertsitate Publikoa. Osasun Zientziak Sailaeu
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.identifier.doi10.1038/s41598-017-09481-x
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/1PE/SAF2014-59340-Ren
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-017-09481-x
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernua, PC025es
dc.contributor.funderUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoaes


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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Except where otherwise noted, this item's license is described as This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.