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

M. Heidari, S.H. H. Gerami, B. Bassett, R.M. M. Graham, Anita C.G. Chua, R. Aryal, Mike J. House, J.F. F. Collingwood, C. Bettencourt, H. Houlden, M. Ryten, J.K. K. Olynyk, Debbie Trinder, D.M. M. Johnstone, E.A. A. Milward

Research output: Contribution to journalArticle

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.
Original languageEnglish
Article numbere1198458
Number of pages11
JournalRare Diseases
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 2016

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Brain Diseases
Myelin Sheath
Iron
Hemochromatosis
Rare Diseases
Transcriptome
Genes
Pelizaeus-Merzbacher Disease
Niemann-Pick Diseases
Charcot-Marie-Tooth Disease
Data Mining
Gene Regulatory Networks
Brain
Peripheral Nervous System Diseases
Basal Ganglia
Multiple Sclerosis
Psychiatry
Gene Expression
Neurodegeneration with brain iron accumulation (NBIA)

Cite this

Heidari, M. ; Gerami, S.H. H. ; Bassett, B. ; Graham, R.M. M. ; Chua, Anita C.G. ; Aryal, R. ; House, Mike J. ; Collingwood, J.F. F. ; Bettencourt, C. ; Houlden, H. ; Ryten, M. ; Olynyk, J.K. K. ; Trinder, Debbie ; Johnstone, D.M. M. ; Milward, E.A. A. / Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases. In: Rare Diseases. 2016 ; Vol. 4, No. 1.
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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.",
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Heidari, M, Gerami, SHH, Bassett, B, Graham, RMM, Chua, ACG, Aryal, R, House, MJ, Collingwood, JFF, Bettencourt, C, Houlden, H, Ryten, M, Olynyk, JKK, Trinder, D, Johnstone, DMM & Milward, EAA 2016, 'Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases' Rare Diseases, vol. 4, no. 1, e1198458. https://doi.org/10.1080/21675511.2016.1198458

Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases. / Heidari, M.; Gerami, S.H. H.; Bassett, B.; Graham, R.M. M.; Chua, Anita C.G.; Aryal, R.; House, Mike J.; Collingwood, J.F. F.; Bettencourt, C.; Houlden, H.; Ryten, M.; Olynyk, J.K. K.; Trinder, Debbie; Johnstone, D.M. M.; Milward, E.A. A.

In: Rare Diseases, Vol. 4, No. 1, e1198458, 01.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases

AU - Heidari, M.

AU - Gerami, S.H. H.

AU - Bassett, B.

AU - Graham, R.M. M.

AU - Chua, Anita C.G.

AU - Aryal, R.

AU - House, Mike J.

AU - Collingwood, J.F. F.

AU - Bettencourt, C.

AU - Houlden, H.

AU - Ryten, M.

AU - Olynyk, J.K. K.

AU - Trinder, Debbie

AU - Johnstone, D.M. M.

AU - Milward, E.A. A.

PY - 2016/1

Y1 - 2016/1

N2 - 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.

AB - 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.

U2 - 10.1080/21675511.2016.1198458

DO - 10.1080/21675511.2016.1198458

M3 - Article

VL - 4

JO - Rare Diseases

JF - Rare Diseases

SN - 2167-5511

IS - 1

M1 - e1198458

ER -