Semax Peptide Binds Copper, Protects Brain Cells from Metal Toxicity

Heavy metal accumulation, particularly of copper(II) ions, can lead to significant cellular damage and is implicated in various neurodegenerative conditions like Alzheimer's disease and Wilson's disease, where copper dyshomeostasis contributes to oxidative stress and neuronal death. Current therapeutic strategies for metal toxicity often involve chelating agents, but these can have side effects or lack specificity. There is a critical need for novel compounds that can safely and effectively mitigate metal-induced cellular damage. This study specifically aimed to investigate the interaction of the peptide Semax with copper(II) ions and its potential to protect cells from metal-induced toxicity.

Spectroscopic analysis confirmed that Semax forms a highly stable complex with copper(II) ions, demonstrating a strong binding affinity with a dissociation constant (Kd) estimated at approximately 50 nM, indicating potent chelation. In the cellular assays, exposure of SH-SY5Y cells to 100 µM CuCl2 alone resulted in a drastic reduction of cell viability by 65% compared to untreated control cells. Co-treatment with Semax significantly and dose-dependently mitigated this copper-induced cytotoxicity. The most significant finding was that Semax at a concentration of 10 µM restored cell viability to 92% of control levels, representing a remarkable 2.6-fold increase in viability compared to cells treated with copper alone (p<0.001). Even at a lower concentration of 1 µM, Semax improved cell viability by 30%, while 50 µM and 100 µM doses maintained viability at 88% and 90% respectively, further highlighting its robust protective capacity. These results suggest Semax effectively sequesters extracellular copper, preventing its intracellular accumulation and subsequent oxidative damage.