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

International Journal of Molecular Sciences
Maialen Palomino-AlonsoEnrique Santamaría

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, suggesti...Continue Reading

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Citations

Sep 6, 2020·International Journal of Molecular Sciences·Mercedes Lachén-MontesEnrique Santamaría
Jun 5, 2020·Translational Neurodegeneration·Isabel Ubeda-BañonAlino Martinez-Marcos
Dec 17, 2018·Journal of Molecular Neuroscience : MN·Thais Guimarães Martins NeryFabio Passetti
Nov 14, 2020·Journal of Proteome Research·Mercedes Lachén-MontesEnrique Santamaría

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Datasets Mentioned

BETA
PXD007795
GSE103835

Methods Mentioned

BETA
transgenic
nuclear translocation
ubiquitination
reverse phase chromatography
acetylation
chips

Software Mentioned

MaxQuant
Ingenuity
QIAGEN
STRING
Image Lab
Perseus
Ingenuity Pathway Analysis ( IPA )
IPA

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