Network-driven proteogenomics unveils an aging-related imbalance in the olfactory IκBα-NFκB p65 complex functionality in Tg2576 Alzheimer’s disease mouse model

Palomino Alonso, Maialen; Lachén Montes, Mercedes; González Morales, Andrea; Ausín, Karina; Pérez Mediavilla, Alberto; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique

Network-driven proteogenomics unveils an aging-related imbalance in the olfactory IκBα-NFκB p65 complex functionality in Tg2576 Alzheimer’s disease mouse model

dc.contributor.author	Palomino Alonso, Maialen
dc.contributor.author	Lachén Montes, Mercedes
dc.contributor.author	González Morales, Andrea
dc.contributor.author	Ausín, Karina
dc.contributor.author	Pérez Mediavilla, Alberto
dc.contributor.author	Fernández Irigoyen, Joaquín
dc.contributor.author	Santamaría Martínez, Enrique
dc.contributor.department	Ciencias de la Salud	es_ES
dc.contributor.department	Osasun Zientziak	eu
dc.contributor.funder	Gobierno de Navarra / Nafarroako Gobernua, PC023-24	es
dc.contributor.funder	Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa	es
dc.date.accessioned	2018-10-02T07:58:04Z
dc.date.available	2018-10-02T07:58:04Z
dc.date.issued	2017
dc.description.abstract	Olfaction is often deregulated in Alzheimer’s disease (AD) patients, and is also impaired in transgenic Tg2576 AD mice, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in aged Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from aged Tg2576 mice (18 months of age) as compared to those of age matched wild-type (WT) littermates. Some over-represented biological functions were directly relevant to neuronal homeostasis and processes of learning, cognition, and behavior. In addition to the modulation of CAMP responsive element binding protein 1 (CREB1) and APP interactomes, an imbalance in the functionality of the IκBα-NFκB p65 complex was observed during the aging process in the OB of Tg2576 mice. At two months of age, the phosphorylated isoforms of olfactory IκBα and NFκB p65 were inversely regulated in transgenic mice. However, both phosphorylated proteins were increased at 6 months of age, while a specific drop in IκBα levels was detected in 18-month-old Tg2576 mice, suggesting a transient activation of NFκB in the OB of Tg2576 mice. Taken together, our data provide a metabolic map of olfactory alterations in aged Tg2576 mice, reflecting the progressive effect of APP overproduction and β-amyloid (Aβ) accumulation on the OB homeostasis in aged stages.	en
dc.description.sponsorship	This 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. PC023-24) and Obra Social la Caixa to Enrique Santamaría. Andrea González-Morales and Karina Ausín were supported by PEJ-2014-A-61949 and PEJ-2014-A-72151 (MINECO). Mercedes Lachén-Montes 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.extent	16 p.
dc.format.mimetype	application/pdf	en
dc.format.mimetype	application/zip	en
dc.identifier.doi	10.3390/ijms18112260
dc.identifier.issn	1661-6596 (Print)
dc.identifier.issn	1422-0067 (Electronic)
dc.identifier.uri	https://academica-e.unavarra.es/handle/2454/30886
dc.language.iso	eng	en
dc.publisher	MDPI	en
dc.relation.ispartof	International Journal of Molecular Sciences, 2017, 18, 2260	en
dc.relation.projectID	info:eu-repo/grantAgreement/MINECO//SAF2014-59340-R/ES/
dc.relation.publisherversion	https://doi.org/10.3390/ijms18112260
dc.rights	© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution.	en
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Tg2576 mice	en
dc.subject	Olfactory bulb	en
dc.subject	Proteogenomics	en
dc.subject	Mass-spectrometry	en
dc.title	Network-driven proteogenomics unveils an aging-related imbalance in the olfactory IκBα-NFκB p65 complex functionality in Tg2576 Alzheimer’s disease mouse model	en
dc.type	info:eu-repo/semantics/article
dc.type.version	info:eu-repo/semantics/publishedVersion
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