Parkinson’s Disease, Environmental Toxins, Intrinsically Disordered Protein
Digital Object Identifier (DOI)
A combination of spectroscopic techniques including atomic force microscopy (AFM) and transmission electron microscopy (TEM), was used to analyze the effect of chemically distinct agrochemicals (pesticides, herbicides, and fungicides) on the in vitro misfolding and aggregation of a presynaptic intrinsically disordered protein α-synuclein. Despite their differences in chemical properties, almost all the compounds screened affected the α-synuclein fibrillation in a concentration-dependent manner. The morphology of the aggregated α-synuclein was characterized by AFM and TEM techniques. In addition to typical fibrils abundantly found at the equilibrium phase, this analysis revealed the existence of a noticeable nonfibrillar fraction where α-synuclein was present as protofilaments, small oligomers, and large oligomeric species. The aggregated α-synuclein samples were separated into soluble and insoluble fractions by ultracentrifugation and subjected to structural and morphological characterization. Attenuated total reflectance Fourier transform infrared spectroscopic analysis showed that the insoluble a-synuclein fractions possessed a high content of ordered β-structure, whereas the β-structure content of the supernatant pool populated by oligomeric species was noticeably lower. This study provides evidence that chemically distinct agrochemicals can directly interact with a-synuclein to induce structural changes and affect the fibrillation process of this important protein.
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Citation / Publisher Attribution
Research and Reports in Biology, v. 2, p. 43-56
Scholar Commons Citation
Silva, Blanca A.; Einarsdóttir, Olöf; Fink, Anthony L.; and Uversky, Vladimir N., "Modulating α-synuclein Misfolding and Fibrillation in Vitro by Agrochemicals" (2011). Molecular Medicine Faculty Publications. 478.