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Ability of selenium species to inhibit metal-induced Aβ aggregation involved in the development of Alzheimer’s disease

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Abstract

Extracellular accumulation of amyloid beta peptide (Aβ) is believed to be one of the main factors responsible for neurodegeneration in Alzheimer’s disease (AD). Metals could induce Aβ aggregation, by their redox activity or binding properties to amyloid β fibrils, leading to their accumulation and deposition outside neurons. For this reason, metal chelation may have an acknowledged part to play in AD prevention and treatment. In the current work, the role of different selenium species, including selenium nanoparticles, in Aβ aggregation, was studied by evaluating their metal-chelating properties and their ability both to inhibit metal-induced Aβ1–42 aggregation fibrils and to disaggregate them once formed. Transition biometals such as Fe(II), Cu(II), and Zn(II) at 50 μM were selected to establish the in vitro models. The DPPH assay was used to determine the antioxidant capacity of the evaluated selenium species. Selenium nanoparticles stabilized with chitosan (Ch-SeNPs) and with both chitosan and chlorogenic acid polyphenol (CGA@ChSeNPs) showed the highest antioxidant properties with EC50 of 0.9 and 0.07 mM, respectively. UV–Vis and d1(UV–Vis) spectra also revealed that selenium species, in particular selenomethionine (SeMet), were able to interact with metals. Regarding Aβ1–42 incubation experiments, Fe(II), Cu(II), and Zn(II) induced Aβ aggregation, in a similar way to most of the evaluated selenium species. However, Ch-SeNPs produced a high inhibition of metal-induced Aβ aggregation, as well as a high disaggregation capacity of Aβ fibrils in both the presence and absence of biometals, in addition to reducing the length and width (20% of reduction in the presence of Zn(II)) of the generated Aβ fibrils.

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Funding

This work was supported by the Community of Madrid (PB2018/BAA-4393, AVANSECAL II-CM), the Spanish Ministry of Economy and Competitiveness (CTQ2017-83569-C2-1-R), and the Complutense University of Madrid (Proyecto Investigación Santander PR26/16-16B-3). David Vicente-Zurdo acknowledges the Spanish Ministry of Science, Innovation and Universities for funding through a pre-doctoral grant (FPU18/00573).

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Vicente-Zurdo, D., Romero-Sánchez, I., Rosales-Conrado, N. et al. Ability of selenium species to inhibit metal-induced Aβ aggregation involved in the development of Alzheimer’s disease. Anal Bioanal Chem 412, 6485–6497 (2020). https://doi.org/10.1007/s00216-020-02644-2

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