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

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Abstract

Alzheimer’s disease (AD), the most prevalent neurodegenerative disease, is characterized by extracellular accumulation of amyloid-beta protein (Aβ), 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 Aβ42 aggregation in TEM studies. These amyloidogenic amino acid enantiomers also widened Aβ42 fibrils up to 437% regarding Aβ42 alone, suggesting that Aβ42 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 Aβ42 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.

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Abbreviations

Aβ42 :

Amyloid-beta protein fragment 1–42

AD:

Alzheimer’s disease

T IC50 :

Stationary time to reach IC50

IC50 :

Half maximal inhibitory concentration

Ch-SeNPs:

Selenium nanoparticles stabilized with chitosan

ROS:

Reactive oxygen species

SeMet:

Selenomethionine

NMDA:

N-Methyl-D-aspartate

TEM:

Transmission electron microscopy

BBB:

Blood–brain barrier

OPA:

ortho-Phthalaldehyde

TBARS:

Thiobarbituric acid reactive substance

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

HFIP:

1,1,1,3,3,3-Hexafluoro-2-propanol

TBA:

Thiobarbituric acid

TCA:

Trichloroacetic acid

EDXS:

Energy-dispersive X-ray spectroscope

UV–Vis:

Ultraviolet–visible

ANOVA:

Analysis of variance

LSD:

Least significant difference

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Acknowledgements

This work was supported by the Spanish Ministry of Science and Innovation (PID2020-114714RB-I00) and the Community of Madrid and European funding from FSE and FEDER programmes (S2018/BAA-4393, PB2018/BAA-4393- AVANSECAL-II-CM). David Vicente-Zurdo acknowledges the Spanish Ministry of Science, Innovation and Universities for funding through a pre-doctoral grant (FPU18/00573). Esther Gómez-Mejía acknowledges Complutense University through a pre-doctoral grant (CT17/17-CT18/17).

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Authors and Affiliations

  1. Analytical Chemistry Department, Faculty of Chemistry, Complutense University of Madrid, 28040, Madrid, Spain

    David Vicente-Zurdo, Sandra Rodríguez-Blázquez, Esther Gómez-Mejía, Noelia Rosales-Conrado, María Eugenia León-González & Yolanda Madrid

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  1. David Vicente-Zurdo
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Contributions

David Vicente-Zurdo: methodology, formal analysis, investigation, data curation, writing—original draft and writing—review and editing; Sandra Rodríguez-Blázquez: methodology, formal analysis, investigation, data curation and writing—review and editing; Esther Gómez-Mejía: methodology and writing—review and editing; Noelia Rosales-Conrado: conceptualization, methodology, investigation and writing—review and editing; María Eugenia León-González: conceptualization, methodology, investigation and writing—review and editing; Yolanda Madrid: conceptualization, methodology, investigation, writing—review and editing and funding acquisition

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Correspondence to David Vicente-Zurdo or Noelia Rosales-Conrado.

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This work received the “Best Poster” award, sponsored by Analytical and Bioanalytical Chemistry, in session S9 “Bioanalytical Chemistry in Health and Food Safety” organized in the framework of the XXXVIII Biennial Meeting of the Spanish Royal Society of Chemistry (RSEQ), 27th–30th June 2022, Granada, Spain.

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Parts of this work were presented at the XXXVIII Biennial Meeting of the Spanish Royal Society of Chemistry (RSEQ), Granada (Spain), in June 2022, and have been awarded with an ABC Best Poster Award.

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Vicente-Zurdo, D., Rodríguez-Blázquez, S., Gómez-Mejía, E. et al. Neuroprotective activity of selenium nanoparticles against the effect of amino acid enantiomers in Alzheimer’s disease. Anal Bioanal Chem 414, 7573–7584 (2022). https://doi.org/10.1007/s00216-022-04285-z

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