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Differential expression and redox proteomics analyses of an Alzheimer disease transgenic mouse model: effects of the amyloid-β peptide of amyloid precursor protein.

Authors: Robinson, R A S  Lange, M B  Sultana, R  Galvan, V  Fombonne, J  Gorostiza, O  Zhang, J  Warrier, G  Cai, J  Pierce, W M  Bredesen, D E  Butterfield, D A 
Citation: Robinson RA, etal., Neuroscience. 2011 Mar 17;177:207-22. doi: 10.1016/j.neuroscience.2011.01.005. Epub 2011 Jan 9.
Pubmed: (View Article at PubMed) PMID:21223993
DOI: Full-text: DOI:10.1016/j.neuroscience.2011.01.005

Among the pathological factors known to be associated with Alzheimer disease (AD), oxidative stress induced by the amyloid-β peptide (Aβ) has been demonstrated to play a key role in human brain and animal models of AD. Recently, we reported elevated levels of oxidative damage in the brain of a transgenic (Tg) AD mouse model with Swedish and Indiana familial AD mutations in human amyloid precursor protein (APP) [PDAPP mice, line J20], as evidenced by increased levels of protein carbonyls, 3-nitrotyrosine, and protein-bound 4-hydroxy-2-nonenal. This oxidative damage was dependent on the methionine 35 residue within the Aβ peptide. Further insight into the molecular pathways affected in this Tg model of AD may be gained with discovery-based proteomics studies; therefore, two-dimensional gel-based expression proteomics was performed to compare differences in brain protein levels of J20 Tg mice with non-transgenic (NTg) littermate controls. Based on our studies, we identified six proteins that had significantly increased levels in J20 Tg relative to NTg mice: calcineurin subunit B type 1, ρ GDP-dissociation inhibitor 1, T-complex protein 1 subunit α A, α-enolase, peptidyl-prolyl cis-trans isomerase (Pin-1), and ATP synthase subunit α mitochondrial. Several of these proteins have previously been implicated in in vitro and in vivo models and subjects with AD. Additionally, using redox proteomics analyses we identified two oxidatively-modified proteins: phosphatidylethanolamine-binding protein 1 and Pin-1 with decreased levels of protein 3-nitrotyrosine in J20 Tg mice relative to NTg. Western blotting and immunoprecipitation analyses were used to validate proteomics results. Overall, these studies provide information about changes in the brain proteome as a result of Aβ deposition and clues with which to further direct studies on elucidating AD pathogenesis.


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CRRD Object Information
CRRD ID: 13830879
Created: 2018-12-07
Species: All species
Last Modified: 2018-12-07
Status: ACTIVE


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