MODULATION BY NEUROMELANIN OF THE AVAILABILITY AND REACTIVITY OF METAL-IONS

Presence of neuromelanin is likely to alter significantly the amount, distribution, reactivity, and consequences of reactivity of metal ions in those parts of the brain that contain neuromelanin. The effects are complex and can be predicted only with detailed knowledge of the system because (1) melanins are strong binders of metal ions and many organic molecules; (2) the effect of binding, depending on the circumstances, can increase or decrease reactivity of metal ions; and (3) melanins can generate and react with oxidation-reduction-active species such as hydrogen peroxide, hydroxyl radicals, superoxide anions, and singlet oxygen. Neuromelanin has some significant differences from most other natural melanins because of its mode of formation (by autooxidation rather than enzymatically) and its composition (it probably is a copolymer derived from dopamine and glutathione). It probably is not possible to understand fully the role of metal ions in oxidative damage in the brain without having an adequate understanding of the structure and reactivity of neuromelanin.