Protein fibrillation is implicated in the pathogenesis of several neurodegenerative diseases like Parkinson’s disease (PD). α-Synuclein (αS) is natively unfolded protein which is involved in pathogenesis of PD. Fibril formation occurs by nucleation dependent kinetics, wherein formation of a critical nucleus is the determinig step, after which fibrillation proceeds rapidly. Nanomaterials have been widely used in great quantities which makes many people more frequently exposed to fabricated nanoparticles (NPs). When NPs are introduced in a living organism they may interact with a variety of different cellular components with yet largely unknown pathological consequences. NPs have enormous surface areas that can access the brain and some of them are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. In our study, we surveyed the effects of three different NPs on αS fibrillation. αS protein expression and purification were performed and fibrils formation was induced at pH 7.4, 37°C, and vigorous shaking in the absence or presence of three types of NPs (TiO2, SiO2, and SnO2). The enhancement of the fluorescence emission of Thioflavin T (ThT) was used to monitor the appearance and growth of fibrils. The adsorption of αS monomers on the surface of NPs, was investigated by tyrosine fluorescence emission measurements. Also transmission electron microscopy (TEM) analysis was performed to explore the ultrastructure of αS aggregates.It was found that TiO2-NPs enhanced αS fibril formation even at concentration of 5 µg/ml while the two other NPs showed no significant effect on the kinetics of fibrillation. Intrinsic tyrosine emission measurements confirmed that the TiO2-NPs interact with αS fibrillation products. It is suggested that TiO2-NPs may enhance the nucleation of αS protein that leads to protein fibrils formation. TEM results are highly correlated with the results of the ThT flourescence assay. Conclusion: The fibrillization process of αS protein is affected by the presence of TiO2-NPs. This finding implicates the potential neurotoxicity of TiO2-NPs, which may be considered as a probable risk for PD.
Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB249
Poster Communications: Acceleration of fibrillation of α-synuclein, a Parkinson’s disease-related protein by TiO2 nanoparticles
M. Nikkhah1, S. Mohammady1
1. Nanobiotechnology, Tarbiat Modares University, Tehran, Iran (the Islamic Republic of).
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Where applicable, experiments conform with Society ethical requirements.