Network-Driven Proteogenomics Unveils an Aging-Related Imbalance in the Olfactory IκBα-NFκB p65 Complex Functionality in Tg2576 Alzheimer’s Disease Mouse Model
Abstract
:1. Introduction
2. Results and Discussion
2.1. Molecular Alterations Detected in the Olfactory Bulb (OB) of 18-Month-Old Tg2576 Mice
2.2. Biological Functions and Neuronal-Specific Processes Altered in the OB of Aged Tg2576 Mice
2.3. Functional Interactome of the hAPPSw Isoform at the Olfactory Level: Characterization of Potential Hubs by Network-Driven Proteogenomics
2.4. An Impairment in the Olfactory IκBα-NFκB p65 Complex Functionality during the Progression of Alzheimer’s Disease (AD) in Tg2576 Mice
3. Materials and Methods
3.1. Materials
3.2. Animals
3.3. Olfactory Proteomics
3.4. OB Transcriptomics
3.5. Bioinformatics
3.6. Immunoblotting Analysis
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
APP | Amyloid precursor protein |
Aβ | β-amyloid |
ERK | Extracellular signal-regulated kinase |
FAK | Focal adhesion kinase |
OB | Olfactory bulb |
MS/MS | Tandem mass-spectrometry |
PDK1 | Phosphoinositide-dependent protein kinase 1 |
PKC | Protein kinase C |
p38 MAPK | p38 Mitogen-activated protein kinase |
WT | Wild-type |
References
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Upstream Regulator | Molecule Type | p-Value | Target Molecules in OB Omics Dataset |
---|---|---|---|
CREB1 | transcription regulator | 0.00000209 | APOE, ARC, EGR1, EGR2, FOSB, GNAL, HLA-A, JUNB, NR4A1, NR4A2, NR4A3, RBP4, SCD, ZDHHC23 |
NFKBIA | transcription regulator | 0.00916 | BCL2A1, CD82, HLA-A, JUNB, MMP15, NID1, NR4A1 |
NFKB1 | transcription regulator | 0.0000748 | APOE, APP, BCL2A1, CD82, EGR1, HLA-DMB, NR4A1, TBX21 |
NFκB (complex) | complex | 0.00174 | APOE, APP, BCL2A1, CD82, EGR1, GFAP, HLA-A, HLA-DMB, JUNB, KLF3 |
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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. https://doi.org/10.3390/ijms18112260
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. International Journal of Molecular Sciences. 2017; 18(11):2260. https://doi.org/10.3390/ijms18112260
Chicago/Turabian StylePalomino-Alonso, Maialen, Mercedes Lachén-Montes, Andrea González-Morales, Karina Ausín, Alberto Pérez-Mediavilla, Joaquín Fernández-Irigoyen, and Enrique Santamaría. 2017. "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 18, no. 11: 2260. https://doi.org/10.3390/ijms18112260