Oxidative Stress Partially Contributes to Iron-Induced Alpha-Synuclein Aggregation in SK-N-SH Cells

Intracellular Lewy body formation is one of the hallmarks of Parkinson's disease (PD). As its main component, aggregated alpha-synuclein is presented in the substantia nigra, the same region iron accumulation occurs. In this study, the relationship between iron and alpha-synuclein aggregation was investigated. In the remaining cells, 1 mmol/l ferric and ferrous iron could induce cell loss in SK-N-SH cells and alpha-synulein aggregation. Pretreatment with 5 mu mol/l vitamin E, a potent intracellular reactive oxygen species (ROS) scavenger could totally abolish ROS formation and cell viability reduction induced by ferric and ferrous iron treatment. However, the intracellular alpha-synuclein aggregation could only be partially alleviated. Due to the predicted iron responsive element (IRE) in the 5'-untranslated region of the human alpha-synuclein mRNA contains, we observed that alpha-synuclein mRNA level was up-regulated in SK-N-SH cells with iron regulatory protein (IRP) knockdown and more alpha-synuclein aggregations were observed in cells. The results suggest that iron-induced intracellular aggregated alpha-synuclein is partially dependent on oxidative stress and iron might also regulate alpha-synuclein aggregation through the IRE/IRP system.