Functional effects of neuromelanin and synthetic melanin in model systems

The function of the dark polymer pigment neuromelanin found in catecholaminergic neurons of the human brain is not understood, especially as most published data are based upon a synthetic model melanin which differs structurally to the native pigment. Nevertheless human neuromelanin has been shown to efficiently bind transition metals such as iron, as well as other potentially toxic molecules. The pigment may have a protective function in the healthy brain by, for example, contributing to iron homeostasis within pigmented nuclei. We have demonstrated that synthetic dopamine melanin stimulates cell damage in both cell lines and primary cells in vitro, an effect associated with increased hydroxyl radical production and apoptosis. In contrast, at low iron concentrations native neuromelanin does not induce cell damage but rather protects cells in culture from oxidative stress. This protective function appears to be lost at high iron concentrations where neuromelanin saturated with iron functions as a source of oxidative load, rather than an iron chelator. Changes to neuromelanin and tissue iron load in Parkinson's disease may decrease the protective potential of the pigment, thus increase the potential for cell damage in this disorder.