Figure 8. Schematic proposing a biphasic effect of oxidative stress on BACE1.

A. Effect of mOS on BACE1 expression. mOS does not alter BACE1 levels but induces its subcellular redistribution to enhance colocalisation. with APP and favour β-CTF production. It may be speculated that this also leads to Aβ production. mOS also induces p38 stress kinase phosphorylation, which can trigger cell survival signaling. B. Effect of severe OS. This increases BACE mRNA and protein expression, thereby increasing APP amyloidogenic processing. MAP kinases also become activated, as well as apoptotic mechanisms. These events cause further cellular accumulation of BACE1, particularly in cellular compartments where APP is present, hence resulting in higher Aβ production and leading to formation of toxic species that induce further OS, by way of a feed-back mechanism.