Copper oxide nanoparticles promote α-synuclein oligomerization and underlying neurotoxicity as a model of Parkinson's disease

Parkinson's disease is associated with the formation of protein aggregates called amyloid fibrils. α-synuclein amyloid accumulation is known to be a key factor in the development of neuronal degenerative diseases in the brain, and exploring some toxic compounds with biomedical application like copper oxide (CuO) nanoparticles that can promote protein aggregation and underlying cytotoxicity are the focus of preventive care studies in Parkinson's disease. Hence, in this study, the effects of synthesized CuO nanoparticles by sol-gel method on the promoting neuronal toxicity of α-synuclein oligomeric structures was investigated by different spectroscopic, cellular, and molecular approaches. For this purpose, the fabricated Cuo nanoparticles were characterized by SEM and TEM techniques. Afterwards, the process of α-synuclein fibrillation was induced and standardized approaches such as fluorescence and circular dichroism spectroscopy as well as TEM analysis were used. The toxicity of α-synuclein oligomeric structures either alone or co-incubated with CuO nanoparticles was then assessed against SH-SY5Y cells using different methods such as MTT, LDH, caspase-3 and qPCR assays. It was observed that spherical-shaped synthesized nanoparticles provide a diameter of about 50 nm. ThT fluorescence, Congo red, circular dichroism and TEM studies showed that CuO nanoparticles promote the fibrillation process of α-synuclein. Also, cellular and molecular assays showed that the relative cytotoxicity of α-synuclein oligomeric structures co-incubated with CuO nanoparticles is more significant than α-synuclein amyloid alone. In conclusion, it can be suggested that CuO nanoparticles increase the detrimental effects of α-synuclein toxic aggregates and can be considered to promote the transmission and spread of α-synuclein aggregation-related cytotoxicity. •Spherical-shaped synthesized nanoparticles provide a diameter of about 50 nm.•CuO nanoparticles promote the fibrillation process of α-synuclein.•Cytotoxicity of α-synuclein oligomers co-incubated with CuO nanoparticles is significant.