Characterization of Uranyl (UO 2 2+ ) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation.
Elina BerntssonFaraz VosoughAndra NoormägiKärt PadariFanny AsplundMaciej GielnikSuman PaulJüri JarvetVello TõuguPer M RoosMaciej KozakAstrid GräslundAndreas BarthMargus PoogaPeep PalumaaSebastian K T S WärmländerPublished in: ACS chemical neuroscience (2023)
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, UO 2 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.
Keyphrases
- heavy metals
- health risk assessment
- amino acid
- health risk
- risk assessment
- quantum dots
- human health
- oxidative stress
- public health
- mental health
- sewage sludge
- air pollution
- mild cognitive impairment
- cognitive decline
- cognitive impairment
- single cell
- cell therapy
- stem cells
- multiple sclerosis
- health information
- ionic liquid
- mesenchymal stem cells
- brain injury
- drinking water
- small molecule
- particulate matter
- subarachnoid hemorrhage
- bone marrow
- protein protein
- metal organic framework
- cerebral ischemia