| First Author | Moskovitz J | Year | 2016 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 310 |
| Issue | 6 | Pages | E388-93 |
| PubMed ID | 26786779 | Mgi Jnum | J:236127 |
| Mgi Id | MGI:5804748 | Doi | 10.1152/ajpendo.00453.2015 |
| Citation | Moskovitz J, et al. (2016) Methionine sulfoxide reductase A affects beta-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease. Am J Physiol Endocrinol Metab 310(6):E388-93 |
| abstractText | Accumulation of oxidized proteins, and especially beta-amyloid (Abeta), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Abeta through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Abeta in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Abeta. Indeed, the novel MsrA-deficient APP mice (APP(+)/MsrAKO) exhibited higher levels of soluble Abeta in brain compared with APP(+) mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP(+)/MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Abeta solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression. |
