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Article

Effects of the Toxic Metals Arsenite and Cadmium on α-Synuclein Aggregation In Vitro and in Cells

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Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden
2
Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden
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Authors to whom correspondence should be addressed.
Academic Editor: Isidro Ferrer
Int. J. Mol. Sci. 2021, 22(21), 11455; https://doi.org/10.3390/ijms222111455
Received: 2 September 2021 / Revised: 21 October 2021 / Accepted: 21 October 2021 / Published: 24 October 2021
(This article belongs to the Special Issue Amyloid Hetero-Aggregation)
Exposure to heavy metals, including arsenic and cadmium, is associated with neurodegenerative disorders such as Parkinson’s disease. However, the mechanistic details of how these metals contribute to pathogenesis are not well understood. To search for underlying mechanisms involving α-synuclein, the protein that forms amyloids in Parkinson’s disease, we here assessed the effects of arsenic and cadmium on α-synuclein amyloid formation in vitro and in Saccharomyces cerevisiae (budding yeast) cells. Atomic force microscopy experiments with acetylated human α-synuclein demonstrated that amyloid fibers formed in the presence of the metals have a different fiber pitch compared to those formed without metals. Both metal ions become incorporated into the amyloid fibers, and cadmium also accelerated the nucleation step in the amyloid formation process, likely via binding to intermediate species. Fluorescence microscopy analyses of yeast cells expressing fluorescently tagged α-synuclein demonstrated that arsenic and cadmium affected the distribution of α-synuclein aggregates within the cells, reduced aggregate clearance, and aggravated α-synuclein toxicity. Taken together, our in vitro data demonstrate that interactions between these two metals and α-synuclein modulate the resulting amyloid fiber structures, which, in turn, might relate to the observed effects in the yeast cells. Whilst our study advances our understanding of how these metals affect α-synuclein biophysics, further in vitro characterization as well as human cell studies are desired to fully appreciate their role in the progression of Parkinson’s disease. View Full-Text
Keywords: α-synuclein; amyloid formation; Parkinson’s disease; arsenic toxicity; cadmium toxicity α-synuclein; amyloid formation; Parkinson’s disease; arsenic toxicity; cadmium toxicity
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MDPI and ACS Style

Lorentzon, E.; Horvath, I.; Kumar, R.; Rodrigues, J.I.; Tamás, M.J.; Wittung-Stafshede, P. Effects of the Toxic Metals Arsenite and Cadmium on α-Synuclein Aggregation In Vitro and in Cells. Int. J. Mol. Sci. 2021, 22, 11455. https://doi.org/10.3390/ijms222111455

AMA Style

Lorentzon E, Horvath I, Kumar R, Rodrigues JI, Tamás MJ, Wittung-Stafshede P. Effects of the Toxic Metals Arsenite and Cadmium on α-Synuclein Aggregation In Vitro and in Cells. International Journal of Molecular Sciences. 2021; 22(21):11455. https://doi.org/10.3390/ijms222111455

Chicago/Turabian Style

Lorentzon, Emma, Istvan Horvath, Ranjeet Kumar, Joana I. Rodrigues, Markus J. Tamás, and Pernilla Wittung-Stafshede. 2021. "Effects of the Toxic Metals Arsenite and Cadmium on α-Synuclein Aggregation In Vitro and in Cells" International Journal of Molecular Sciences 22, no. 21: 11455. https://doi.org/10.3390/ijms222111455

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