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Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes
Abstract
Information on the molecular distribution and ageing trend of brain iron in post-mortem material from normal subjects is scarce. Because it is known that neuromelanin and ferritin form stable complexes with iron(III), in this study we measured the concentration of iron, ferritin and neuromelanin in substantia nigra from normal subjects, aged between 1 and 90 years, dissected post mortem. Iron levels in substantia nigra were 20 ng/mg in the first year of life, had increased to 200 ng/mg by the fourth decade and remained stable until 90 years of age. The H-ferritin concentration was also very low (29 ng/mg) during the first year of life but increased rapidly to values of approximately 200 ng/mg at 20 years of age, which then remained constant until the eighth decade of life. L-Ferritin also showed an increasing trend during life although the concentrations were approximately 50% less than that of H-ferritin at each age point. Neuromelanin was not detectable during the first year, increased to approximately 1000 ng/mg in the second decade and then increased continuously to 3500 ng/mg in the 80th year. A Mössbauer study revealed that the high-spin trivalent iron is probably arranged in a ferritin-like iron--oxyhydroxide cluster form in the substantia nigra. Based on this data and on the low H- and L-ferritin content in neurones it is concluded that neuromelanin is the major iron storage in substantia nigra neurones in normal individuals.
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“In the substantia nigra, ferritin heavy chain and ferritin light chain concentrations increase with age, whereas these are constant in the locus coeruleus; therefore iron could contribute to neurodegeneration in the substantia nigra more than in the locus coeruleus.5,6”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [5]
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Mukherjee, S., & Panda, D. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00377 · Cited by 40
Binding of Metal Ions to Melanin and Their Effects on the Aerobic Reactivity¶
Hong, L., Liu, Y., & Simon, J. D. (2004) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2004.tb00117.x · Cited by 40
Shukla, D., Goel, A., Mandal, P. K., Joon, S., Punjabi, K., Arora, Y., Kumar, R., Mehta, V. S., Singh, P., Maroon, J. C., et al. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00717 · Cited by 39
Amit, T., Bar‐Am, O., Mechlovich, D., Kupershmidt, L., Youdim, M. B. H., & Weinreb, O. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.05.026 · Cited by 38
Capucciati, A., Zucca, F. A., Monzani, E., Zecca, L., Casella, L., & Hofer, T. (2021) · Antioxidants · doi:10.3390/antiox10060824 · Cited by 36
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Investigation of the effects of copper ions on protein aggregation using a model system
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Postnatal decrease in substantia nigra echogenicity
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The Iron Chelator Deferiprone Improves the Phenotype in a Mouse Model of Tauopathy
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RETRACTED: The Iron Chelator Deferiprone Improves the Phenotype in a Mouse Model of Tauopathy1
Rao, S. S., Portbury, S. D., Lago, L., Bush, A. I., & Adlard, P. A. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200551 · Cited by 36
RetractedIron Redox Chemistry and Implications in the Parkinson’s Disease Brain
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Mariani, S., Ventriglia, M., Simonelli, I., Spalletta, G., Bucossi, S., Siotto, M., Assogna, F., Melgari, J.-M., Vernieri, F., & Squitti, R. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00037 · Cited by 35
Altered Processing of β-Amyloid in SH-SY5Y Cells Induced by Model Senescent Microglia
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Richter, D., Katsanos, A. H., Schroeder, C., Tsivgoulis, G. K., Paraskevas, G. P., Müller, T. H., Alexandrov, A. V., Gold, R., Tönges, L., & Krogias, C. (2019) · Cells · doi:10.3390/cells9010002 · Cited by 35
Viktorínová, A., & Ďurfinová, M. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135627 · Cited by 35
Metadata
- Authors
- Zecca, L., Gallorini, M., Schünemann, V., Trautwein, A. X., Gerlach, M., Riederer, P., Vezzoni, P., & Tampellini, D.
- Affiliations
- Institute of Biomedical Technologies (IT)
- University of Pavia (IT)
- University of Lübeck (DE)
- University of Würzburg (DE)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2001-03-15
- Volume
- 76
- Issue
- 6
- Pages
- 1766-1773
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1601438958
- Cited by
- 401
- References
- 61
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 11 · 2023: 13 · 2022: 19 · 2021: 25 · 2020: 13 · 2019: 20 · 2018: 23 · 2017: 18 · 2016: 19 · 2015: 10 · 2014: 14 · 2013: 17 · 2012: 14
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Fondazione Cariplo
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- brain iron, substantia nigra, neuromelanin, ferritin, iron storage, aging, neurodegeneration, high-spin iron, postmortem brain
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Ferritins, Humans, Infant, Iron, Melanins, Middle Aged, Nerve Degeneration, Reference Values, Substantia Nigra
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