Development of potential iron chelators for the treatment of Friedreich's ataxia: ligands that mobilize mitochondrial iron

被引：79

作者：

Richardson, DR

Mouralian, C

Ponka, P

Becker, E

机构：

[1] Heart Res Inst, Iron Metab & Chelat Grp, Sydney, NSW 2050, Australia

[2] Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2001年 / 1536卷 / 2-3期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

chelator; desferrioxamine; Friedreich's ataxia; iron; iron overload disease; pyridoxal isonicotinoyl hydrazone;

D O I：

10.1016/S0925-4439(01)00041-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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页码：133 / 140

页数：8

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