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

Extracellular accumulation of amyloid beta peptide (Abeta) is believed to be one of the main factors responsible for neurodegeneration in Alzheimer's disease (AD). Metals could induce Abeta aggregation, by their redox activity or binding properties to amyloid beta 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 Abeta aggregation, was studied by evaluating their metal-chelating properties and their ability both to inhibit metal-induced Abeta1-42 aggregation fibrils and to disaggregate them once formed. Transition biometals such as Fe(II), Cu(II), and Zn(II) at 50 muM 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 d(1)(UV-Vis) spectra also revealed that selenium species, in particular selenomethionine (SeMet), were able to interact with metals. Regarding Abeta1-42 incubation experiments, Fe(II), Cu(II), and Zn(II) induced Abeta aggregation, in a similar way to most of the evaluated selenium species. However, Ch-SeNPs produced a high inhibition of metal-induced Abeta aggregation, as well as a high disaggregation capacity of Abeta 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 Abeta fibrils. Graphical abstract.