Neuroprotective activity of selenium nanoparticles against the effect of amino acid enantiomers in Alzheimer's disease

Alzheimer's disease (AD), the most prevalent neurodegenerative disease, is characterized by extracellular accumulation of amyloid-beta protein (A beta), which is believed to be the very starting event of AD neurodegeneration. In this work, D-Phe, D-Ala, and D-Glu amino acids, which are the non-occurring enantiomeric form in the human body, and also D-Asp and DL-SeMet, have proved to be amyloidogenic regarding A beta(42) aggregation in TEM studies. These amyloidogenic amino acid enantiomers also widened A beta(42) fibrils up to 437% regarding A beta(42) alone, suggesting that A beta(42) aggregation is enantiomerically dependent. To inhibit enantiomeric-induced amyloid aggregation, selenium nanoparticles stabilized with chitosan (Ch-SeNPs) were successfully synthesized and employed. Thus, Ch-SeNPs reduced and even completely inhibited A beta(42 )aggregation produced in the presence of some amino acid enantiomers. In addition, through UV-Vis spectroscopy and fluorescence studies, it was deduced that Ch-SeNPs were able to interact differently with amino acids depending on their enantiomeric form. On the other hand, antioxidant properties of amino acid enantiomers were evaluated by DPPH and TBARS assays, with Tyr enantiomers being the only ones showing antioxidant effect. All spectroscopic data were statistically analysed through experimental design and response surface analysis, showing that the interaction between the Ch-SeNPs and the amino acids studied was enantioselective and allowing, in some cases, to establish the concentration ratios in which this interaction is maximum.

Automated summary

This study revealed the significant impact of rare amino acid enantiomers on the aggregation of beta-amyloid protein in Alzheimer's disease. The synthesis of selenium nanoparticles stabilized with chitosan successfully inhibited the amyloid aggregation induced by these enantiomers. Additionally, the study demonstrated that the interaction between chitosan-stabilized selenium nanoparticles and different amino acid enantiomers varied, and only Tyr enantiomers exhibited antioxidant effects.