Effects of Edaravone on Amyloid-β Precursor Protein Processing in SY5Y-APP695 Cells

Abstract

Previous reports have revealed that reactive oxygen species (ROS) is involved in the development of Alzheimer's disease (AD), and recent studies indicate that free radical-generating systems can regulate amyloid-β precursor protein (APP) processing. Edaravone is a novel free radical scavenger currently used to reduce cerebral damages after acute cerebral infarction. In the present study, we used SH-SY5Y cells stably transfected with the human "Swedish" APP mutation APP695 (SY5Y-APP695swe) as an in vitro model to investigate the effect of edaravone on APP processing. The result showed that edaravone treatment for 24h down-regulated β-amyloid (Aβ) production in a dose-dependent manner. Moreover, edaravone modulated APP processing by increasing α-secretase-derived APP fragments and decreasing β-secretase-derived APP fragments. In addition, the mRNA and protein levels of insulin degrading enzyme (IDE) and neprilysin (NEP), two key Aβ degrading enzymes, were not changed after edaravone administration. Taken together, our data suggested that edaravone played an important role in regulating Aβ production by enhancing the non-amyloidogenic pathway and inhibiting the amyloidogenic pathway. Thus, edaravone may be potentially useful for treating Alzheimer's disease (AD).