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

Uranium (U) is naturally present in ambient air, water,and soil,and depleted uranium (DU) is released into the environment via industrialand military activities. While the radiological damage from U is ratherwell understood, less is known about the chemical damage mechanisms,which dominate in DU. Heavy metal exposure is associated with numeroushealth conditions, including Alzheimer's disease (AD), themost prevalent age-related cause of dementia. The pathological hallmarkof AD is the 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 increaseA & beta; production, and these metals bind to A & beta; peptides andmodulate their aggregation. The possible effects of U in AD pathologyhave been sparsely studied. Here, we use biophysical techniques tostudy in vitro interactions between A & beta; peptides and uranyl ions,UO2 (2+), of DU. We show for the first time thaturanyl ions bind to A & beta; peptides with affinities in the micromolarrange, induce structural changes in A & beta; monomers and oligomers,and inhibit A & beta; fibrillization. This suggests a possible linkbetween AD and U exposure, which could be further explored by cell,animal, and epidemiological studies. General toxic mechanisms of uranylions could be modulation of protein folding, misfolding, and aggregation.