Fig. 1.

Iron, dopamine, and α-syn in dopaminergic neurons. Under physiological conditions, iron is essential for some biological processes, while contributing to a pro-oxidant environment in cells. DA is in balance between the free cytoplasmic form and the stored vesicular form and participates in both enzymatic and non-enzymatic metabolic processes. Alpha-syn functions in membrane-associated processes and regulates vesicular trafficking in its native form. In the disease state of PD, elevated iron elicits oxidative damage, accelerates DA-derived metabolic toxicity, and aggravates α-syn dysfunction by promoting its expression and aggregation. Alpha-syn-induced defects in vesicular incorporation retain free DA while overexpressed α-syn increases ferrireductase activity and ferrous iron levels. DA promotes α-syn aggregation and the metabolic products react with iron. These manifest a toxic vicious cycle among iron, DA, and α-syn in PD