RESUMEN
In general, Cu(II) is the critical factor in catalyzing reactive oxygen species (ROS) production and accelerating amyloid-ß (Aß) oligomer formation in Alzheimer's disease (AD). Natural chelating agents with good biocompatibility and appropriate binding affinity with Cu(II) have emerged as potential candidates for AD therapy. Herein, we tested the capability of guluronic acid disaccharide (Di-GA), a natural chelating agent with the moderate association affinity to Cu(II), in inhibiting ROS production and Aß oligomer formation. The results showed that Di-GA was capable of chelating with Cu(II) and reducing ROS production, even in solutions containing Fe(II), Zn(II), and Aß. In addition, Di-GA can also capture Cu(II) from Cu-Aß complexes and decrease Aß oligomer formation. The cellular results confirmed that Di-GA prevented SH-SY5Y cells from ROS and Aß oligomer damage by reducing the injury of ROS and Aß oligomers on cell membrane and decreasing their intracellular damage on mitochondria. Notably, the slightly higher efficiency of Di-GA in chelating with Cu(I) than Cu(II) can be benefit for its in vivo applications, as Cu(I) is not only the most active but also the special intermediate specie during ROS production process. All of these results proved that Di-GA could be a promising marine drug candidate in reducing copper-related ROS damage and Aß oligomer toxicity associated with AD.