Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson's disease.
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 Fe2+ 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 (Fe3+) 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.
Faucheux
Baptiste A
BA
INSERM U.289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, F-75013 Paris, France. baptiste.faucheux@chups.jussieu.fr
Martin
Marie-Elise
ME
Beaumont
Carole
C
Hauw
Jean-Jacques
JJ
Agid
Yves
Y
Hirsch
Etienne C
EC
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005290:Ferric Compounds / Q000032:analysis; D006801:Humans; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008543:Melanins / Q000378:metabolism*; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000473:pathology*; D011540:Prussian Blue Reaction; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology*
D005290:Ferric Compounds; D046911:Macromolecular Substances; D008543:Melanins; C014121:neuromelanin; D007501:Iron