Chelating and antioxidant properties of l-Dopa containing tetrapeptide for the treatment of neurodegenerative diseases

Neurodegenerative diseases share a common pathogenetic mechanism involving aggregation and deposition of misfolded proteins, oxidative stress, metal dyshomeostasis, and glutamate exicitotoxicity, which lead to progressive dysfunction of central nervous system (CNS). A potential strategy to counterac...

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Veröffentlicht in:Neuropeptides (Edinburgh) 2018-10, Vol.71, p.11-20
Hauptverfasser: Cacciatore, Ivana, Marinelli, Lisa, Di Stefano, Antonio, Di Marco, Valerio, Orlando, Giustino, Gabriele, Mirko, Gatta, Daniela Maria Pia, Ferrone, Alessio, Franceschelli, Sara, Speranza, Lorenza, Patruno, Antonia
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Sprache:eng
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Zusammenfassung:Neurodegenerative diseases share a common pathogenetic mechanism involving aggregation and deposition of misfolded proteins, oxidative stress, metal dyshomeostasis, and glutamate exicitotoxicity, which lead to progressive dysfunction of central nervous system (CNS). A potential strategy to counteract these deleterious events at neuronal level is represented by the employment of a novel class of multi-target therapeutic agents that selectively and simultaneously hit these targets In this paper, we report the metal binding and antioxidant properties of a novel metal-protein attenuating peptide, GSH-LD, a tetrapeptide obtained by linking glutathione, a well-known antioxidant tripeptide, to L-Dopa. Results demonstrated that GSH-LD possesses chelating capabilities in order to selectively target the excess of metals without interfere with metal-containing antioxidant enzymes. Moreover, antioxidant assays revealed a large contribution of GSH-LD to restore the antioxidant defences of damaged neuronal cells [Display omitted] •GSH-LD as potential tool to treat neurodegenerative disorders•GSH-LD as chelating agent of metals•GSH-LD may reduce oxidative stress in neurodegenerative diseases
ISSN:0143-4179
1532-2785
DOI:10.1016/j.npep.2018.06.002