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Iron deficiency in parkinsonism : region-specific iron dysregulation in Parkinson's disease and multiple system atrophy
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Visanji, Naomi P., Collingwood, Joanna F., Finnegan, Mary E., Tandon, Anurag , House, Emily and Hazrati, Lili-Naz (2013) Iron deficiency in parkinsonism : region-specific iron dysregulation in Parkinson's disease and multiple system atrophy. Journal of Parkinson's Disease, Volume 3 (Number 4). pp. 523-537. doi:10.3233/JPD-130197
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Official URL: http://dx.doi.org/10.3233/JPD-130197
Abstract
Alpha synuclein pathology is widespread and found in diverse cell types in multiple system atrophy (MSA) as compared to Parkinson's disease (PD). The reason for this differential distribution is unknown. Regional differences in the distribution of iron are associated with neurodegenerative diseases, and here we characterize the relationship between iron homeostasis proteins and regional concentration, distribution and form of iron in MSA and PD. In PD substantia nigra, tissue iron and expression of the iron export protein ferroportin increased, while the iron storage protein ferritin expression was unchanged. In the basis pontis of MSA cases, increased total iron concentration coupled with a disproportionate increase in ferritin in dysmorphic microglia and a reduction in ferroportin expression. This is supported by isothermal remanent magnetisation evidence consistent with elevated concentrations of ferritin-bound iron in MSA basis pontis. Conventional opinion holds that excess iron is involved in neurodegeneration. Our data support that this may be the case in PD. While region-specific changes in iron are evident in both PD and MSA, the mechanisms of iron dysregulation appear quite distinct, with a failure to export iron from the MSA basis pontis coupling with significant intracellular accumulation of ferritin iron. This pattern also occurs, to a lesser extent, in the MSA putamen. Despite the excess tissue iron, the manner of iron dysregulation in MSA is reminiscent of changes in anemia of chronic disease, and our preliminary data, coupled with the widespread pathology and involvement of multiple cell types, may evidence a deficit in bioavailabile iron.
| Item Type: | Journal Article | ||||
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| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | ||||
| Divisions: | Faculty of Science > Engineering | ||||
| Library of Congress Subject Headings (LCSH): | Parkinson's disease, Nervous system -- Degeneration, Brain -- Degeneration, Iron deficiency diseases | ||||
| Journal or Publication Title: | Journal of Parkinson's Disease | ||||
| Publisher: | IOS Press | ||||
| ISSN: | 1877-7171 | ||||
| Official Date: | 2013 | ||||
| Dates: |
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| Volume: | Volume 3 | ||||
| Number: | Number 4 | ||||
| Page Range: | pp. 523-537 | ||||
| DOI: | 10.3233/JPD-130197 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access | ||||
| Funder: | Parkinson Society Canada, Engineering and Physical Sciences Research Council (EPSRC), Research Councils UK (RCUK), Alzheimer's Society (AS), Canadian Institutes of Health Research (CIHR), Advantage West Midlands (AWM), European Regional Development Fund (ERDF) | ||||
| Grant number: | EP/D066654/1 (EPSRC), MOP 84501 (CIHR) |
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