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bioRxiv · 10.1101/2023.03.29.534802

Characterization of uranyl ion binding to amyloid beta (Aβ) peptides: effects on Aβ structure and aggregation

Berntsson, E.·Vosough, F.·Noormagi, A.·Padari, K.·Asplund, F.·Gielnik, M.·Paul, S.·Jarvet, J.·Tougu, V.·Roos, P. M.·Kozak, M.·Graslund, A.·Barth, A.·Pooga, M.·Palumaa, P.·Warmlander, S. K. T. S.
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Abstract

AbstractUranium (U) is naturally present in ambient air, water, and soil, and depleted uranium (DU) is released into the environment via industrial and military activities. While the radiological damage from U is rather well understood, less is known about the chemical damage mechanisms, which dominate in DU. Heavy metal exposure is associated with numerous health conditions including Alzheimers disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is deposition of amyloid plaques, consisting mainly of amyloid-{beta} (A{beta}) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric A{beta} aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase A{beta} production, and these metals bind to A{beta} peptides and modulate their aggregation. Possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to study in vitro interactions between A{beta} peptides and uranyl ions, UO22+, of DU. We show for the first time that uranyl ions bind to A{beta} peptides with affinities in the micromolar range, induce structural changes in A{beta} monomers and oligomers, and inhibit A{beta} fibrillization. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation.

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Berntsson, E., Vosough, F., Noormagi, A., Padari, K., Asplund, F., Gielnik, M., Paul, S., Jarvet, J., Tougu, V., Roos, P. M., Kozak, M., Graslund, A., Barth, A., Pooga, M., Palumaa, P., Warmlander, S. K. T. S.. 2023-04-01. Characterization of uranyl ion binding to amyloid beta (Aβ) peptides: effects on Aβ structure and aggregation. https://doi.org/10.1101/2023.03.29.534802

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