Influence of neuromelanin on oxidative pathways within the human substantia nigra

Neuromelanin (NM) is a dark-coloured pigment produced in the dopaminergic neurons of the human substantia nigra (SN). The function of NM within the pigmented neurons is unknown but other melanins are believed to play a protective role via attenuation of free radical damage. Experimental evidence suggests that NM may also exhibit this characteristic, possibly by directly inactivating free radical species or via its ability to chelate transition metals, such as iron. Increased tissue iron, however, may saturate iron-chelating sites on NM and a looser association between iron and NM may result in an increased, rather than decreased, production of free radical species. The death of NM-pigmented neurons in Parkinson's disease (PD) is associated with both a measurable increase in tissue iron concentrations and indices of free radical mediated damage, suggesting that NM is involved in the aetiology of this disorder. As yet, it is unknown whether NM in the parkinsonian brain differs to that found in healthy tissue and thus may fulfil a different role within this tissue.