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

Rare diseases (Austin, Tex.) Pub Date : 2016-06-22 eCollection Date: 2016-01-01 DOI:10.1080/21675511.2016.1198458
Moones Heidari, Sam H Gerami, Brianna Bassett, Ross M Graham, Anita C G Chua, Ritambhara Aryal, Michael J House, Joanna F Collingwood, Conceição Bettencourt, Henry Houlden, Mina Ryten, John K Olynyk, Debbie Trinder, Daniel M Johnstone, Elizabeth A Milward
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引用次数: 10

Abstract

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.

Abstract Image

涉及铁和髓磷脂的病理关系可能构成一种连接各种罕见和常见脑部疾病的共同机制。
我们之前在血色素沉着Hfe (-/-) xTfr2 (mut)小鼠模型中证明了髓鞘结构和相关细胞中的脑铁水平升高。这伴随着一组髓磷脂相关基因的表达改变,包括一组与罕见疾病家族“脑铁积累神经变性”(NBIA)相关的基因。扩展的数据挖掘和本体论分析现在已经确定了额外的髓磷脂相关转录组变化,以响应脑铁负荷。小鼠转录组变化与正常和NBIA基底神经节中人类髓鞘相关基因表达网络之间的一致性证明了潜在的临床相关性。这些分析表明,除其他外,与各种罕见的中枢性低髓鞘性白质营养不良和周围神经病变(包括pelizaeus - merzbacer样疾病和Charcot-Marie-Tooth病)以及与其他罕见的神经系统疾病(如Niemann-Pick病)相关的基因。这一发现可能有助于了解铁和髓磷脂在血色素沉着症、多发性硬化症和各种精神疾病等更常见疾病中的相互关系。
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