Copper oxide nanoparticles promote amyloid-β-triggered neurotoxicity through formation of oligomeric species as a prelude to Alzheimer's diseases.

Abstract

Protein oligomerization is involved in the progression of Alzheimer's disease (AD). In general, a particle that can accelerate protein oligomerization should be considered a toxic material. Several studies reported the progress of nanoparticles (NPs) such as copper oxide (CuO) in biomedical platforms, however, they may have the ability to promote the protein oligomerization process. Here, we aimed to study the effect of CuO NPs on amyloid β1-42 (Aβ1-42) oligomerization and relevant neurotoxicity. CuO NPs were synthesized by precipitation technique and characterized by several methods such as ThT, Congo red, CD spectroscopic methods, and TEM imaging. The outcomes indicated that the fabricated CuO NPs with a size of around 50 nm led to a remarkable acceleration in Aβ1-42 oligomerization in a concentration-dependent manner through shortening the nucleation step and promoting the fibrillization rate. Moreover, cellular assays revealed that Aβ1-42 oligomers aged with CuO NPs were more toxic than Aβ1-42 oligomers untreated against SH-SY5Y cells in triggering cell mortality, membrane leakage, oxidative stress, and apoptosis. In conclusion, this study provides important information about the adverse effects of CuO NPs against proteins in the central nervous system to promote the formation of cytotoxic oligomers.