Antioxidants (Mar 2023)

Interaction and Redox Chemistry between Iron, Dopamine, and Alpha-Synuclein C-Terminal Peptides

  • Fabio Schifano,
  • Simone Dell’Acqua,
  • Stefania Nicolis,
  • Luigi Casella,
  • Enrico Monzani

DOI
https://doi.org/10.3390/antiox12040791
Journal volume & issue
Vol. 12, no. 4
p. 791

Abstract

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α-Synuclein (αS), dopamine (DA), and iron have a crucial role in the etiology of Parkinson’s disease. The present study aims to investigate the interplay between these factors by analyzing the DA/iron interaction and how it is affected by the presence of the C-terminal fragment of αS (Ac-αS119–132) that represents the iron-binding domain. At high DA:Fe molar ratios, the formation of the [FeIII(DA)2]– complex prevents the interaction with αS peptides, whereas, at lower DA:Fe molar ratios, the peptide is able to compete with one of the two coordinated DA molecules. This interaction is also confirmed by HPLC-MS analysis of the post-translational modifications of the peptide, where oxidized αS is observed through an inner-sphere mechanism. Moreover, the presence of phosphate groups in Ser129 (Ac-αSpS119–132) and both Ser129 and Tyr125 (Ac-αSpYpS119–132) increases the affinity for iron(III) and decreases the DA oxidation rate, suggesting that this post-translational modification may assume a crucial role for the αS aggregation process. Finally, αS interaction with cellular membranes is another key aspect for αS physiology. Our data show that the presence of a membrane-like environment induced an enhanced peptide effect over both the DA oxidation and the [FeIII(DA)2]– complex formation and decomposition.

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