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 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.
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Investigations have shown an increase in redox-active iron associated with neuromelanin in substantia nigra neurons of patients with Parkinson's disease, probably as a result of decreased ferritin synthesis.
“Investigations have shown an increase in redox-active iron associated with neuromelanin in substantia nigra neurons of patients with Parkinson’s disease, probably as a result of decreased ferritin synthesis.”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [124]
High concentrations of iron detected in the substantia nigra of individuals with Parkinson's disease might exceed the iron-buffering capacity of complexes, such as neuromelanin and ferritin, and could induce neurotoxicity.
“High concentrations of iron detected in the substantia nigra of individuals with Parkinson’s disease might exceed the iron-buffering capacity of complexes, such as neuromelanin and ferritin, and could induce neurotoxicity.124”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [124]
Increased redox-active iron is higher in patients with the most severe neuronal loss and is absent in neurons without neuromelanin.
“Increased redox-active iron is higher in patients with the most severe neuronal loss and is absent in neurons without neuromelanin.122–124”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [124]
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- Authors
- Faucheux, B. A., Martin, M., Beaumont, C., Hauw, J., Agid, Y., & Hirsch, E. C.
- Affiliations
- Inserm (FR)
- Pitié-Salpêtrière Hospital (FR)
- Corresponding author
- Faucheux, Baptiste A.
- ORCID
- Hauw, Jean‐Jacques
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2003-08-11
- Volume
- 86
- Issue
- 5
- Pages
- 1142-1148
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1558984540
- Cited by
- 229
- References
- 41
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 12 · 2023: 8 · 2022: 12 · 2021: 9 · 2020: 4 · 2019: 14 · 2018: 6 · 2017: 9 · 2016: 15 · 2015: 11 · 2014: 17 · 2013: 9 · 2012: 12
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- neuromelanin, redox-active iron, Parkinson's disease, substantia nigra pars compacta, dopaminergic neurons, oxidative stress, non-heme iron, hydroxyl radicals, iron overload, neuronal loss
- MeSH terms
- Aged, Aged, 80 and over, Female, Ferric Compounds, Humans, Iron, Male, Melanins, Oxidation-Reduction, Parkinson Disease, Prussian Blue Reaction, Substantia Nigra, Macromolecular Substances
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