Mitochondrial methionine sulfoxide reductase B2 links oxidative stress to Alzheimer's disease-like pathology.

Mitochondrial methionine sulfoxide reductase B2 links oxidative stress to Alzheimer's disease-like pathology. Exp Neurol. 2019 May 09;: Authors: Xiang XJ, Song L, Deng XJ, Tang Y, Min Z, Luo B, Wen QX, Li KY, Chen J, Ma YL, Zhu BL, Yan Z, Chen GJ Abstract Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cell from oxidative stress. The antioxidant activity suggests that MSRB2 may play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that in APP/PS1 mice, an animal model of AD, MSRB2 protein levels were decreased in the hippocampus at both young (6 mon) and old (18 mon) age, and in the cortex only at an old age, respectively. In HEK293 cells that stably express human full-length β-amyloid precursor protein (APP, HEK/APP), MSRB2 reduced the protein and mRNA levels of APP and β-amyloid converting enzyme 1 (BACE1), and the consequent amyloid beta peptide (Aβ) 1-40 and Aβ1-42 levels. MSRB2 overexpression or knockdown also oppositely affected Tau phosphorylation at selective sites, with the concomitant alteration of the phosphorylated extracellular signal regulated kinase (p-ERK) and AMP-activated protein kinase (p-AMPK) levels. Moreover, in cells treated with long-term (24 h) hydrogen peroxide, the alterations of APP processing and Tau phosphorylation were reversed by MSRB2 overexpression. We further found that MSRB2-mediated regulation of APP transcription involved JNK and ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research