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Int. J. Mol. Sci. 2017, 18(11), 2260; https://doi.org/10.3390/ijms18112260

Network-Driven Proteogenomics Unveils an Aging-Related Imbalance in the Olfactory IκBα-NFκB p65 Complex Functionality in Tg2576 Alzheimer’s Disease Mouse Model

1
Clinical Neuroproteomics Group, Navarrabiomed, Departamento de Salud, Universidad Pública de Navarra, 31008 Pamplona, Spain
2
Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Departamento de Salud, Universidad Pública de Navarra, 31008 Pamplona, Spain
3
Instituto de Investigación Sanitaria de Navarra (IdiSNA), Navarra Institute for Health Research, 31008 Pamplona, Spain
4
Neurobiology of Alzheimer’s Disease, Neurosciences Division, Center for Applied Medical Research (CIMA), Department of Biochemistry, University of Navarra, 31008 Pamplona, Spain
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 27 September 2017 / Revised: 23 October 2017 / Accepted: 25 October 2017 / Published: 27 October 2017
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Aging and Age-Related Disorders)
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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. View Full-Text
Keywords: Tg2576 mice; olfactory bulb; proteogenomics; mass-spectrometry Tg2576 mice; olfactory bulb; proteogenomics; mass-spectrometry
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Palomino-Alonso, M.; Lachén-Montes, M.; González-Morales, A.; Ausín, K.; Pérez-Mediavilla, A.; Fernández-Irigoyen, J.; Santamaría, E. Network-Driven Proteogenomics Unveils an Aging-Related Imbalance in the Olfactory IκBα-NFκB p65 Complex Functionality in Tg2576 Alzheimer’s Disease Mouse Model. Int. J. Mol. Sci. 2017, 18, 2260.

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