Sequestration of iron by Lewy bodies in Parkinson's disease
Abstract
Central to the oxidative stress hypothesis of Parkinson's disease (PD) pathogenesis is the ability of iron to generate hydroxyl radicals via the Fenton reaction, and the consistent demonstration of iron elevation in the pars compacta region of the substantia nigra. However, uncertainty exists as to whether the excess iron exists in a state suitable for redox chemistry. Here, using a method we developed that detects redox-active iron in situ, we were able to demonstrate strong labeling of Lewy bodies in substantia nigra pars compacta neurons in PD. In contrast, cortical Lewy bodies in cases of Lewy body variant of Alzheimer's disease were unstained. While the presence of elevated iron in PD substantiates the oxidative stress hypothesis, one must remember that these are viable neurons, indicating that Lewy bodies may act to sequester iron in PD brains in a protective, rather than degenerative, mechanism. The absence of redox-active iron in neocortical Lewy bodies highlights a fundamental difference between cortical and brain stem Lewy bodies.
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Redox-active iron accumulates in Lewy bodies in the substantia nigra of individuals with Parkinson's disease.
“Redox-active iron accumulates in Lewy bodies in the substantia nigra of individuals with Parkinson’s disease.115”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [115]
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- Authors
- Castellani, R. J., Siedlak, S. L., Perry, G., & Smith, M. A.
- Affiliations
- Case Western Reserve University (US)
- Venue
- Acta Neuropathologica
- Published
- 2000-08-03
- Volume
- 100
- Issue
- 2
- Pages
- 111-114
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2017268270
- Cited by
- 265
- References
- 22
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 13 · 2020: 11 · 2019: 10 · 2018: 12 · 2017: 14 · 2016: 12 · 2015: 12 · 2014: 10 · 2013: 13 · 2012: 12
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag009287-08)
- National Institute on Aging (AG 09287)
- National Institute of Neurological Disorders and Stroke (NS 38648, R01NS038648)
- 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
- Parkinson's disease, Lewy bodies, iron sequestration, redox-active iron, oxidative stress hypothesis, Fenton reaction, hydroxyl radicals, substantia nigra pars compacta, cortical Lewy bodies
- MeSH terms
- Aged, Aged, 80 and over, Cerebral Cortex, Ferric Compounds, Ferrous Compounds, Histocytochemistry, Humans, Immunohistochemistry, Iron, Mesencephalon, Middle Aged, Parkinson Disease, Tissue Distribution, Lewy Bodies, Lewy Body Disease
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