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

Document Type: Research Paper

Authors

Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-175 Iran

Abstract

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 fi brillation in the brain by decreasing the lag time for nucleation. Protein fi brillation is implicated in the pathogenesis of the several neurodegenerative diseases such as Parkinson’s disease (PD). α-Synuclein (αS) is natively an unfolded protein which is involved in the pathogenesis of PD. In the present study, we have analyzed the eff ects of three diff erent NPs on αS fi brillation.
Materials and Methods: αS protein expression and purifi cation was done and fi brils formation was induced
in the absence or presence of the three types of NPs (i. e., TiO2, SiO2, and SnO2). The enhancement of the
fl uorescence emission of Thiofl avin T (ThT) and transmission electron microscopy (TEM) were used to monitor the appearance and growth of the fi brils. The adsorption of αS monomers on the surface of NPs was investigated by tyrosine fl uorescence emission measurements.
Results: We found that TiO2-NPs enhances αS fi bril formation even at a concentration of 5 μg.mL-1, while
the two other NPs show no signifi cant eff ect on the kinetics of the fi brillation. Intrinsic tyrosine emission
measurement has confi rmed that the TiO2-NPs interact with αS fi brillation products. It is suggested that TiO2-NPs may enhance the nucleation of αS protein that leads to protein fi bril formation.
Conclusion: The fi brillization process of αS protein is profoundly aff ected by the presence of TiO2-NPs. This
fi nding unveils the neurotoxicity potential of the TiO2-NPs, which may be considered as a probable risk for PD.

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