Neuromelanin associated redox‐active iron is increased in the substantia nigra of patients with Parkinson's disease

Abstract Degeneration of dopaminergic neurones during Parkinson's disease is most extensive in the subpopulation of melanized‐neurones located in the substantia nigra pars compacta. Neuromelanin is a dark pigment produced in the dopaminergic neurones of the human substantia nigra and has the ability to bind a variety of metal ions, especially iron. Post‐mortem analyses of the human brain have established that oxidative stress and iron content are enhanced in association with neuronal death. As redox‐active iron (free Fe 2+ form) and other transition metals have the ability to generate highly reactive hydroxyl radicals by a catalytic process, we investigated the redox activity of neuromelanin (NM)‐aggregates in a group of parkinsonian patients, who presented a statistically significant reduction (− 70%) in the number of melanized‐neurones and an increased non‐heme (Fe 3+ ) iron content as compared with a group of matched‐control subjects. The level of redox activity detected in neuromelanin‐aggregates was significantly increased (+ 69%) in parkinsonian patients and was highest in patients with the most severe neuronal loss. This change was not observed in tissue in the immediate vicinity of melanized‐neurones. A possible consequence of an overloading of neuromelanin with redox‐active elements is an increased contribution to oxidative stress and intraneuronal damage in patients with Parkinson's disease.