Characterization of Uranyl (UO2 2+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation

• Published in: ACS chemical neuroscience 2023-08, Vol.14 (15), p.2618-2633
• Main Authors: Berntsson, Elina, Vosough, Faraz, Noormägi, Andra, Padari, Kärt, Asplund, Fanny, Gielnik, Maciej, Paul, Suman, Jarvet, Jüri, Tõugu, Vello, Roos, Per M., Kozak, Maciej, Gräslund, Astrid, Barth, Andreas, Pooga, Margus, Palumaa, Peep, Wärmländer, Sebastian K. T. S.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid; amyloid aggregation; Amyloid beta-Peptides - metabolism; Animals; heavy metal toxicity; Ions - chemistry; Medicin och hälsovetenskap; metal-protein binding; neurodegeneration; Uranium
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.3c00130

Uranium (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 Alzheimer’s disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is the deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric Aβ aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase Aβ production, and these metals bind to Aβ peptides and modulate their aggregation. The possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to study in vitro interactions between Aβ peptides and uranyl ions, UO2 2+, of DU. We show for the first time that uranyl ions bind to Aβ peptides with affinities in the micromolar range, induce structural changes in Aβ monomers and oligomers, and inhibit Aβ fibrillization. This suggests a possible link between AD and U exposure, which could be further explored by cell, animal, and epidemiological studies. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation.