Dysregulated iron metabolism in the choroid plexus in fragile X-associated tremor/ataxia syndrome.
Dysregulated iron metabolism in the choroid plexus in fragile X-associated tremor/ataxia syndrome.
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DOI：
10.1016/j.brainres.2014.11.058
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发表时间：
2015-02-19
期刊：
影响因子：
2.9
通讯作者：
Martinez-Cerdeno, Veronica
中科院分区：
文献类型：
--
作者：
Ariza, Jeanelle;Steward, Craig;Rueckert, Flora;Widdison, Matt;Coffman, Robert;Afjei, Atiyeh;Noctor, Stephen C.;Hagerman, Randi;Hagerman, Paul;Martinez-Cerdeno, Veronica
脆性X相关震颤/共济失调综合征（FXTAS）是一种迟发性神经退行性疾病，与FMR 1基因的前突变等位基因相关，其特征为进行性动作震颤、步态共济失调和认知能力下降。最近对FXTAS中线粒体功能障碍的研究表明，铁失调可能是疾病发病机制的一个组成部分。我们检验了铁失调是FXTAS致病过程的一部分的假设。我们分析了FXTAS和对照受试者的死后脉络丛，发现FXTAS中铁在基质中积聚，上皮细胞中转铁蛋白水平降低，转铁蛋白受体1分布从基底外侧膜（对照）转移到主要细胞内位置（FXTAS）。此外，上皮细胞内的膜铁蛋白和铜蓝蛋白显着减少。这些改变不仅对理解FXTAS的病理生理学有意义，而且对开发可能结合选择性铁螯合的新临床治疗也有意义。
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene that is characterized by progressive action tremor, gait ataxia, and cognitive decline. Recent studies of mitochondrial dysfunction in FXTAS have suggested that iron dysregulation may be one component of disease pathogenesis. We tested the hypothesis that iron dysregulation is part of the pathogenic process in FXTAS. We analyzed postmortem choroid plexus from FXTAS and control subjects, and found that in FXTAS iron accumulated in the stroma, transferrin levels were decreased in the epithelial cells, and transferrin receptor 1 distribution was shifted from the basolateral membrane (control) to a predominantly intracellular location (FXTAS). In addition, ferroportin and ceruloplasmin were markedly decreased within the epithelial cells. These alterations have implications not only for understanding the pathophysiology of FXTAS, but also for the development of new clinical treatments that may incorporate selective iron chelation.
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影响因子：
5.3
作者：
Chonchaiya W;Au J;Schneider A;Hessl D;Harris SW;Laird M;Mu Y;Tassone F;Nguyen DV;Hagerman RJ
通讯作者：
Hagerman RJ
DOI：
10.1097/00004703-200604002-00012
发表时间：
2006-04-01
影响因子：
2.4
作者：
Farzin, Faraz;Perry, Hazel;Hagerman, Randi
通讯作者：
Hagerman, Randi
DOI：
10.3109/10715768609051634
发表时间：
1986-01-01
期刊：
Free radical research communications
影响因子：
--
作者：
Grootveld, M;Halliwell, B
通讯作者：
Halliwell, B
DOI：
10.1111/j.1440-1681.2011.05661.x
发表时间：
2012-08-01
影响因子：
2.9
作者：
Anderson, Gregory J.;Wang, Fudi
通讯作者：
Wang, Fudi
影响因子：
120.7
作者：
Jacquemont, S;Hagerman, RJ;Hagerman, PJ
通讯作者：
Hagerman, PJ