The enigma of neuromelanin in Parkinson's disease substantia nigra.

The function of neuromelanin accumulation in the nigrostriatal dopamine neurons remains uncertain. Nevertheless, it is recognized that neuromelanin disappearance parallels the loss of dopamine neurons in Parkinson's disease, suggesting its participation in nigral cell death. It has been well known for some years that in systemic tissues melanin is a double-edged sword. On the one hand it can act as an antioxidant, but in the presence of transitional metals (primarily, iron) and drugs it promotes the formation of reactive oxygen free radicals. It is now apparent that synthetic dopamine-melanin and neuromelanin exhibit similar properties in vitro and nigrostriatal dopamine neuron co-culture studies. Thus, the identification of ionic iron in dopamine neurons of Parkinson's disease zona compacta and its association with neuromelanin has conferred a cytotoxic property to neuromelanin. This may explain the reported vulnerability of substantia nigra dopamine neurons in Parkinson's disease.