The β-amyloid (Aβ) peptide plays a key role in the pathogenesis of Alzheimer's disease. The methionine (Met) residue at position 35 in Aβ C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aβ most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aβ25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4-, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•-). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO3•- causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS•+). The formation of this transient reactive intermediate during Aβ oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation.

One- and two-electron oxidations of β-amyloid25-35 by carbonate radical anion (CO3•-) and peroxymonocarbonate (HCO4-): role of sulfur in radical reactions and peptide aggregation / Francioso, A.; Conrado, A. B.; Blarzino, C.; Foppoli, C.; Montanari, E.; Dinarelli, S.; Giorgi, A.; Mosca, L.; Fontana, M.. - In: MOLECULES. - ISSN 1420-3049. - 25:4(2020). [10.3390/molecules25040961]

One- and two-electron oxidations of β-amyloid25-35 by carbonate radical anion (CO3•-) and peroxymonocarbonate (HCO4-): role of sulfur in radical reactions and peptide aggregation

Francioso A.
Primo
;
Blarzino C.;Foppoli C.;Montanari E.;Dinarelli S.;Giorgi A.;Mosca L.
;
Fontana M.
2020

Abstract

The β-amyloid (Aβ) peptide plays a key role in the pathogenesis of Alzheimer's disease. The methionine (Met) residue at position 35 in Aβ C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aβ most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aβ25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4-, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•-). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO3•- causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS•+). The formation of this transient reactive intermediate during Aβ oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation.
2020
Carbonate radical anion; methionine sulfoxide; peroxymonocarbonate; reactive sulfur species; sulfur centered radical; sulfur radical cation; β-amyloid
01 Pubblicazione su rivista::01a Articolo in rivista
One- and two-electron oxidations of β-amyloid25-35 by carbonate radical anion (CO3•-) and peroxymonocarbonate (HCO4-): role of sulfur in radical reactions and peptide aggregation / Francioso, A.; Conrado, A. B.; Blarzino, C.; Foppoli, C.; Montanari, E.; Dinarelli, S.; Giorgi, A.; Mosca, L.; Fontana, M.. - In: MOLECULES. - ISSN 1420-3049. - 25:4(2020). [10.3390/molecules25040961]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1380417
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