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Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases

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Heidari, Moones, Gerami, Sam H., Bassett, Brianna, Graham, Ross M., Chua, Anita C. G., Aryal, Ritambhara, House, Michael J., Collingwood, Joanna F., Bettencourt, Conceição, Houlden, Henry, Ryten, Mina, Olynyk, John K., Trinder, Debbie, Johnstone, Daniel M. and Milward, Elizabeth A. (2016) Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases. Rare Diseases, 4 (1). e1198458. doi:10.1080/21675511.2016.1198458 ISSN 2167-5511.

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Official URL: http://dx.doi.org/10.1080/21675511.2016.1198458

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Abstract

We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe−/−xTfr2mut mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes causatively linked to the rare disease family ‘neurodegeneration with brain iron accumulation’ (NBIA). Expanded data mining and ontological analyses have now identified additional myelin-related transcriptome changes in response to brain iron loading. Concordance between the mouse transcriptome changes and human myelin-related gene expression networks in normal and NBIA basal ganglia testifies to potential clinical relevance. These analyses implicate, among others, genes linked to various rare central hypomyelinating leukodystrophies and peripheral neuropathies including Pelizaeus-Merzbacher-like disease and Charcot-Marie-Tooth disease as well as genes linked to other rare neurological diseases such as Niemann-Pick disease. The findings may help understand interrelationships of iron and myelin in more common conditions such as hemochromatosis, multiple sclerosis and various psychiatric disorders.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH): Hemochromatosis, Myelin proteins, Nervous system -- Degeneration
Journal or Publication Title: Rare Diseases
Publisher: Routledge
ISSN: 2167-5511
Official Date: 2016
Dates:
DateEvent
2016Published
22 June 2016Available
1 June 2016Accepted
22 February 2016Submitted
Volume: 4
Number: 1
Article Number: e1198458
DOI: 10.1080/21675511.2016.1198458
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 1 August 2016
Date of first compliant Open Access: 1 August 2016
Funder: National Health and Medical Research Council (Australia) (NHMRC) , Fremantle Hospital Medical Research Foundation, Australian Society for Medical Research, Engineering and Physical Sciences Research Council (EPSRC), Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England)
Grant number: 572601 (NHMRC) , 1042370 (NHMRC) , 1020437 (NHMRC) , 1078747 (NHMRC), EP/D066654/1 (EPSRC), MR/J004758/1 (MRC), WT104033/Z/14/Z (WT)
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