Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion...

Alzheimer's disease (AD) is the most common neurodegenerative disorder associated with cognitive decline and loss of memory. It is postulated that the generation of reactive oxygen species (ROS) in Fenton-like reaction connected with Cu(II)/Cu(I) redox cycling of the Cu(II)-aβ complex can play a key role in the molecular mechanism of neurotoxicity in AD. Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic regulatory peptide that possesses a high affinity for Cu(II) ions. The ability of the peptide Semax to inhibit the copper-catalyzed oxidation of aβ was studied in vitro and discussed. The results indicate that Semax is able to extract Cu(II) from Cu(II)-aβ species as well as to influence the redox cycling of the Cu(II)-aβ complex and decrease the level of associated ROS production. Finally, our data suggest that Semax shows cytoprotective properties for SH-SY5Y cells against oxidative stress induced by copper-catalyzed oxidation of the aβ peptide. This study provides valuable insights into the potential role of Semax in neurodegenerative disorders and into the design of new compounds with therapeutic potential for AD.