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

Abstract

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.

Keywords: Antioxidant; Metal dyshomeostasis; Metal-protein attenuating compounds; Neurodegenerative disease; Oxidative stress.