Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson's disease
Identifieur interne : 003243 ( Main/Exploration ); précédent : 003242; suivant : 003244Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson's disease
Auteurs : Baptiste A. Faucheux [France] ; Marie-Elise Martin [France] ; Carole Beaumont [France] ; Jean-Jacques Hauw [France] ; Yves Agid [France] ; Etienne C. Hirsch [France]Source :
- Journal of neurochemistry [ 0022-3042 ] ; 2003.
Descripteurs français
- Pascal (Inist)
- Wicri :
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Cell death, Degeneration, Dopaminergic neuron, Female, Ferric Compounds (analysis), Free radical, Human, Humans, Iron, Iron (analysis), Iron (metabolism), Locus niger, Macromolecular Substances, Male, Melanins (metabolism), Neuromelanin, Oxidation-Reduction, Oxidative stress, Oxygen, Parkinson Disease (pathology), Parkinson disease, Prussian Blue Reaction, Substantia Nigra (metabolism), Substantia Nigra (pathology).
- MESH :
- chemical , analysis : Ferric Compounds, Iron.
- chemical , metabolism : Iron, Melanins.
- metabolism : Substantia Nigra.
- pathology : Parkinson Disease, Substantia Nigra.
- Aged, Aged, 80 and over, Female, Humans, Macromolecular Substances, Male, Oxidation-Reduction, Prussian Blue Reaction.
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 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.
Affiliations:
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Le document en format XML
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<term>Aged, 80 and over</term>
<term>Cell death</term>
<term>Degeneration</term>
<term>Dopaminergic neuron</term>
<term>Female</term>
<term>Ferric Compounds (analysis)</term>
<term>Free radical</term>
<term>Human</term>
<term>Humans</term>
<term>Iron</term>
<term>Iron (analysis)</term>
<term>Iron (metabolism)</term>
<term>Locus niger</term>
<term>Macromolecular Substances</term>
<term>Male</term>
<term>Melanins (metabolism)</term>
<term>Neuromelanin</term>
<term>Oxidation-Reduction</term>
<term>Oxidative stress</term>
<term>Oxygen</term>
<term>Parkinson Disease (pathology)</term>
<term>Parkinson disease</term>
<term>Prussian Blue Reaction</term>
<term>Substantia Nigra (metabolism)</term>
<term>Substantia Nigra (pathology)</term>
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<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Ferric Compounds</term>
<term>Iron</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Iron</term>
<term>Melanins</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Substantia Nigra</term>
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<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term>
<term>Substantia Nigra</term>
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<term>Locus niger</term>
<term>Dégénérescence</term>
<term>Neurone dopaminergique</term>
<term>Stress oxydatif</term>
<term>Mort cellulaire</term>
<term>Radical libre</term>
<term>Oxygène</term>
<term>Parkinson maladie</term>
<term>Homme</term>
<term>Neuromélanine</term>
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<front><div type="abstract" xml:lang="en">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<sup>2+</sup>
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<sup>3+</sup>
) 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.</div>
</front>
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<name sortKey="Faucheux, Baptiste A" sort="Faucheux, Baptiste A" uniqKey="Faucheux B" first="Baptiste A." last="Faucheux">Baptiste A. Faucheux</name>
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<name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name>
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