The toxicity of amyloid beta peptide on SH-SY5Y cells in the presence and absence of copper ions and metal chelators

Alzheimer s disease (AD) is one of the most common diseases of the aging population and is mainly caused by the aggregation of amyloid beta peptide (Aβ42) in the brain of aged individuals. The pathological hallmarks of the disease are the appearance of extracellular amyloid plaques and intracellular neurofibrillary tangles formed by tau protein. Dyshomeostasis of metal ions, that not only affect the aggregation of Aβ42 but also might cause oxidative stress, are also reported in the AD. According to these observations, chelation therapy has been proposed as a possible intervention to restore the metal ion imbalance and to reduce the toxicity caused by interactions between metal ions and Aβ42. In this study, SH-SY5Y human neuroblastoma cells have been used to study the effect of copper ion on the viability of SH-SY5Y cells, in the presence of Aβ42, at three different concentrations (at 0.5, 1 and 2 stoichiometries relative to Aβ42). The chelation effects of ethylenediaminetetraacetic (EDTA) and clioquinol (CQ) were also examined. The results indicated that sub-stoichiometric concentrations of copper could induce amyloid fibrillation and oligomerization and reduced cellular viability was observed. At stochiometric and superstoichiometric concentrations of copper ions, it was observed that Aβ42 aggregation was reduced and cell viability increased. In the next part of this study, effects of chelators, EDTA and CQ, were studied. When chelators were also present in the cell culture medium, the stoichiometry of copper ion relative to Aβ42was adjusted to 0.5. Our results showed that both EDTA and CQ reduced the strengthening effect of copper on aggregation of Aβ42 and cell viability was increased. Our results could be considered promising in chelation therapy approach in the AD.