CALL FOR PAPERS Mitochondrial Dynamics and Oxidative Stress Methionine sulfoxide reductase A affects -amyloid solubility and mitochondrial function in a mouse model of Alzheimer’s disease

Moskovitz J, Du F, Bowman CF, Yan SS. Methionine sulfoxide reductase A affects -amyloid solubility and mitochondrial function in a mouse model of Alzheimer’s disease. Am J Physiol Endocrinol Metab 310: E388–E393, 2016. First published January 19, 2016; doi:10.1152/ajpendo.00453.2015.—Accumulation of oxidized proteins, and especially -amyloid (A ), 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 A through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and A 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 A . Indeed, the novel MsrA-deficient APP mice (APP /MsrAKO) exhibited higher levels of soluble A 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 A solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression.