Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases.
MetadataShow full item record
This open access article is distributed under the Creative Commons license https://creativecommons.org/licenses/by-nc/3.0/
We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe (-/-) xTfr2 (mut) 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.
Showing items related by title, author, creator and subject.
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric featuresHeidari, M.; Johnstone, D.; Bassett, B.; Graham, Ross; Chua, A.; House, M.; Collingwood, J.; Bettencourt, C.; Houlden, H.; Ryten, M.; Olynyk, John; Trinder, D.; Milward, E. (2016)The ‘neurodegeneration with brain iron accumulation’ (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with ...
Johnstone, D.; Graham, Ross; Trinder, D.; Delima, R.; Riveros, C.; Olynyk, John; Scott, R.; Moscato, P.; Milward, E. (2012)Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which ...
Brain transcriptome perturbations in the transferrin receptor 2 mutant mouse support the case for brain changes in iron loading disorders, including effects relating to long-term depression and long-term potentiationAcikyol, B.; Graham, Ross; Trinder, D.; House, M.; Olynyk, John; Scott, R.; Milward, E; Johnstone, D. (2013)Iron abnormalities within the brain are associated with several rare but severe neurodegenerative conditions. There is growing evidence that more common systemic iron loading disorders such as hemochromatosis can also ...