TiO2 Nanoparticles as Potential Promoting Agents of Fibrillation of α-Synuclein, a Parkinson's Disease-Related Protein

Background: In recent years, nanomaterials have been widely used in large quantities which make people be more frequently exposed to the chemically synthesized nanoparticles (NPs). When NPs are introduced into an organism, they may interact with a variety of cellular components with yet largely unknown pathological consequences. Objective: It was found that NPs enhance the rate of protein fibrillation in the brain by decreasing the lag time for nucleation. Protein fibrillation is implicated in the pathogenesis of the several neurodegenerative diseases such as Parkinson's disease (PD). alpha-Synuclein (alpha S) is natively an unfolded protein which is involved in the pathogenesis of PD. In the present study, we have analyzed the effects of three different NPs on alpha S fibrillation. Materials and Methods: alpha S protein expression and purification was done and fibrils formation was induced in the absence or presence of the three types of NPs (i. e., TiO2, SiO2, and SnO2). The enhancement of the fluorescence emission of Thioflavin T (ThT) and transmission electron microscopy (TEM) were used to monitor the appearance and growth of the fibrils. The adsorption of alpha S monomers on the surface of NPs was investigated by tyrosine fluorescence emission measurements. Results: We found that TiO2-NPs enhances alpha S fibril formation even at a concentration of 5 mu g.mL(-1), while the two other NPs show no significant effect on the kinetics of the fibrillation. Intrinsic tyrosine emission measurement has confirmed that the TiO2-NPs interact with alpha S fibrillation products. It is suggested that TiO2-NPs may enhance the nucleation of alpha S protein that leads to protein fibril formation. Conclusion: The fibrillization process of alpha S protein is profoundly affected by the presence of TiO2-NPs. This finding unveils the neurotoxicity potential of the TiO2-NPs, which may be considered as a probable risk for PD.