Effects of titanium dioxide nanoparticles on α-synuclein aggregation and the ubiquitin-proteasome system in dopaminergic neurons

Abstract

Dopaminergic neurons (PC12 cells) were treated with different doses of titanium dioxide nanoparticles (TiO₂-NPs), to investigate their effects on α-Synuclein (α-Syn) aggregation and their mechanism of action. Western blotting and immunofluorescent staining were performed. Exposure to TiO₂-NPs increased α-Syn expression (p < 0.05) and induced dose-dependent α-Syn aggregation. Pretreatment with N-acetylcysteine partially inhibited α-Syn expression induced by a 200 μg/ml dose of TiO₂-NPs. TiO₂-NPs reduced the expressions of parkin and ubiquitin C-terminal hydrolase protein, and were associated with oxidative stress in PC12 cells. Dysfunction of the ubiquitin-proteasome system also contributed to α-Syn aggregation. The potentially neurotoxic TiO₂-NPs may cause Parkinson's disease.

Keywords::

• dopaminergic neuron
• titanium dioxide nanoparticles
• ubiquitin-proteasome pathway
• α-synuclein

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by grants from the Natural Science Foundation of China (No. 31200756) and Science and Technology Research Program for Colleges and Universities in Shandong Province, China (No. J12LK54).