Lack of up-regulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients with Parkinson's disease
Abstract
Dopaminergic neurones degenerate during Parkinson's disease and cell loss is most extensive in the subpopulation of melanized neurones located in the substantia nigra pars compacta. Iron accumulation, together with a lack of up-regulation of the iron-storing protein, ferritin, has been reported and may contribute to increased oxidative stress in this region. We investigated the binding activity of iron regulatory protein-1 (IRP1) to the iron-responsive element that precludes ferritin mRNA translation, in the substantia nigra of a group of parkinsonian patients who presented a statistically significant reduction in the number of nigral melanized-neurones and an increased iron content, together with unchanged H-ferritin and L-ferritin subunit levels as compared to matched controls. The levels of ferritin mRNAs and the binding activity of IRP1 to the iron-responsive element of ferritin mRNA did not differ significantly between the two groups. Moreover, there was no detectable contribution of the iron regulatory protein-2 (IRP2) binding activity. No change in IRP1 control of ferritin mRNA translation explains the lack of up-regulation of ferritin expression in cytoplasmic extracts of SNpc that would be normally expected with cytosolic iron accumulation. The data of this study do not favor changes in transcription and post-transcriptional regulation of ferritin expression in Parkinson's disease and suggest a 'compartmentalized' iron accumulation.
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Reduced ferritin production might be caused by sustained IRP1 activity noted in post-mortem Parkinson's disease brains, which would reduce ferritin synthesis.
“Reduced ferritin production might be caused by sustained IRP1 activity, noted in post-mortem Parkinson’s disease brains, which would reduce ferritin synthesis.121”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [121]
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- Authors
- Faucheux, B. A., Martin, M., Beaumont, C., Hunot, S., Hauw, J., Agid, Y., & Hirsch, E. C.
- Affiliations
- Inserm (FR)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2002-10
- Volume
- 83
- Issue
- 2
- Pages
- 320-330
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1544137195
- Cited by
- 116
- References
- 53
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 6 · 2012: 7
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Parkinson's disease, substantia nigra pars compacta, ferritin, iron regulatory protein 1, IRP2, iron-responsive element, iron accumulation, oxidative stress, post-transcriptional regulation
- MeSH terms
- Aged, Aged, 80 and over, Cell Count, Cytoplasm, Female, Ferritins, Humans, Male, Mesencephalon, Middle Aged, Parkinson Disease, Protein Binding, RNA, Messenger, Substantia Nigra, Reproducibility of Results, Up-Regulation, In Situ Hybridization, Protein Subunits, Electrophoretic Mobility Shift Assay, Iron Regulatory Protein 1, Iron Regulatory Protein 2
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