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铁:神经退行性疾病药物干预的新靶点。

Iron: a new target for pharmacological intervention in neurodegenerative diseases.

作者信息

Whitnall Megan, Richardson Des R

机构信息

Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia.

出版信息

Semin Pediatr Neurol. 2006 Sep;13(3):186-97. doi: 10.1016/j.spen.2006.08.008.

Abstract

Iron (Fe) is an essential element that is imperative for the redox-driven processes of oxygen transport, electron transport, and DNA synthesis. However, in the absence of appropriate storage or chelation, excess-free Fe readily participates in the formation of toxic-free radicals, inducing oxidative stress and apoptosis. A growing body of evidence suggests that Fe may play some role in neurodegenerative diseases such as Huntington disease, Alzheimer's disease, Parkinson's disease, and particularly Friedreich's ataxia. This review examines the role of Fe in the pathology of these conditions and the potential use of Fe chelators as therapeutic agents for the treatment of neurodegenerative disorders. Consideration is given to the features that comprise a clinically successful Fe chelator, with focus on the development of ligands such as desferrioxamine, clioquinol, pyridoxal isonicotinoyl hydrazone, and other novel aroylhydrazones.

摘要

铁(Fe)是一种必需元素,对于氧运输、电子传递和DNA合成等由氧化还原驱动的过程至关重要。然而,在缺乏适当储存或螯合的情况下,过量的游离铁很容易参与有毒自由基的形成,诱导氧化应激和细胞凋亡。越来越多的证据表明,铁可能在神经退行性疾病如亨廷顿病、阿尔茨海默病、帕金森病,尤其是弗里德赖希共济失调中发挥一定作用。本文综述了铁在这些疾病病理过程中的作用,以及铁螯合剂作为治疗神经退行性疾病治疗药物的潜在用途。文中考虑了构成临床上成功的铁螯合剂的特征,重点关注了去铁胺、氯碘羟喹、吡啶醛异烟酰腙等配体以及其他新型芳酰腙的开发。

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