Development of potential iron chelators for the treatment of Friedreich's ataxia: ligands that mobilize mitochondrial iron
Development of potential iron chelators for the treatment of Friedreich's ataxia: ligands that mobilize mitochondrial iron
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DOI：
10.1016/s0925-4439(01)00041-2
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发表时间：
2001-05-31
影响因子：
6.2
通讯作者：
Becker, E
中科院分区：
文献类型：
--
作者：
Richardson, DR;Mouralian, C;Becker, E
弗里德赖希共济失调症（FA）是一种严重的神经退行性疾病，是由于线粒体内铁（Fe）超载引起的。一种治疗干预可能是开发一种螯合剂，可以去除线粒体铁。我们建立了唯一一个表征良好的哺乳动物线粒体铁过载模型，以检验2-吡啶基甲醛异烟碱酰腙（PCIH）类新型螯合剂的铁螯合效果。在这个模型中，我们利用血红素合成抑制剂琥珀酰丙酮处理的网状红细胞，导致线粒体铁负载。我们的实验表明，与去铁胺相反，几种PCIH类似物在从负载铁-59的网状细胞中动员铁-59方面表现出非常高的活性。考虑到这些配体治疗FA的潜力，在动物身上的进一步研究显然是有必要的。(C) 2001 Elsevier Science B.V.版权所有
Friedreich's ataxia (FA) is a crippling neurodegenerative disease that is due to iron (Fe) overload within the mitochondrion. One therapeutic intervention may be the development of a chelator that could remove mitochondrial Fe. We have implemented the only well characterized model of mammalian mitochondrial Fe overload to examine the Fe chelation efficacy of novel chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) class. In this model we utilize reticulocytes treated with the haem synthesis inhibitor succinylacetone which results in mitochondrial Fe-loading. Our experiments demonstrate that in contrast to desferrioxamine, several of the PCIH analogues show very high activity at mobilizing Fe-59 from Fe-59-loaded reticulocytes. Further studies on these ligands in animals are clearly warranted considering their potential to treat FA. (C) 2001 Elsevier Science B.V. All rights reserved.