Neurodegenerative diseases and therapeutic strategies using iron chelators
Neurodegenerative diseases and therapeutic strategies using iron chelators
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DOI：
10.1016/j.jtemb.2014.12.012
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发表时间：
2015-01-01
影响因子：
3.5
通讯作者：
Crichton, Robert R.
中科院分区：
文献类型：
--
作者：
Ward, Roberta J.;Dexter, David T.;Crichton, Robert R.
这篇综述将总结我们目前的知识状态，涉及铁在各种神经系统疾病和潜在的治疗与铁螯合剂，以延缓疾病的进展。我们首先简要讨论了金属离子在脑功能中的作用，然后概述了过渡金属离子（如铁和铜）通过产生活性氧和氮物质引发神经退行性变的方式。这导致蛋白质错误折叠、淀粉样蛋白的产生以及包含在包涵体中的不溶性蛋白质聚集体的形成。这将激活小胶质细胞，导致神经炎症。神经炎症在神经退行性疾病的进展中起重要作用，活化的小胶质细胞释放促炎细胞因子导致细胞损失。金属参与帕金森氏症和阿尔茨海默氏症以及弗里德赖希共济失调和多发性硬化症的证据将被提出。这些神经退行性疾病的铁螯合治疗试验的初步结果将进行审查。(C)2015爱思唯尔有限公司All rights reserved.
This review will summarise the current state of our knowledge concerning the involvement of iron in various neurological diseases and the potential of therapy with iron chelators to retard the progression of the disease. We first discuss briefly the role of metal ions in brain function before outlining the way by which transition metal ions, such as iron and copper, can initiate neurodegeneration through the generation of reactive oxygen and nitrogen species. This results in protein misfolding, amyloid production and formation of insoluble protein aggregates which are contained within inclusion bodies. This will activate microglia leading to neuroinflammation. Neuroinflammation plays an important role in the progression of the neurodegenerative diseases, with activated microglia releasing pro-inflammatory cytokines leading to cellular cell loss. The evidence for metal involvement in Parkinson's and Alzheimer's disease as well as Friedreich's ataxia and multiple sclerosis will be presented. Preliminary results from trials of iron chelation therapy in these neurodegenerative diseases will be reviewed. (C) 2015 Elsevier GmbH. All rights reserved.