Current status of metals as therapeutic targets in Alzheimer's disease
Current status of metals as therapeutic targets in Alzheimer's disease
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DOI：
10.1046/j.1532-5415.2003.51368.x
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发表时间：
2003-08-01
影响因子：
6.3
通讯作者：
Doraiswamy, PM
中科院分区：
文献类型：
--
作者：
Finefrock, AE;Bush, AI;Doraiswamy, PM
越来越多的证据表明，β-淀粉样蛋白与铜、铁和锌之间的相互作用与阿尔茨海默病(AD)的病理生理学有关。已经检测到铜、铁和锌的显著动态平衡失调，这些金属的管理不善会导致β淀粉样蛋白沉淀和神经毒性。螯合剂为铜、铁代谢紊乱所致的神经毒性提供了一种潜在的治疗方案。目前，铜锌螯合剂CLIOQOL代表了一种潜在的治疗途径，它不仅可以抑制β-淀粉样蛋白的神经毒性，还可以逆转新皮质β-淀粉样蛋白的积聚。补充B-12的CLOQOL的II期双盲临床试验即将公布，结果令人振奋。本文综述了过渡金属在淀粉样蛋白形成中的作用，并回顾了螯合疗法作为AD治疗的潜在前景。
There is accumulating evidence that interactions between beta-amyloid and copper, iron, and zinc are associated with the pathophysiology of Alzheimer's disease (AD). A significant dyshomeostasis of copper, iron, and zinc has been detected, and the mismanagement of these metals induces beta-amyloid precipitation and neurotoxicity. Chelating agents offer a potential therapeutic solution to the neurotoxicity induced by copper and iron dyshomeostasis. Currently, the copper and zinc chelating agent clioquinol represents a potential therapeutic route that may not only inhibit beta-amyloid neurotoxicity, but may also reverse the accumulation of neocortical beta-amyloid. A Phase II double-blind clinical trial of clioquinol with B-12 supplementation will be published soon, and the results are promising. This article summarizes the role of transition metals in amyloidgenesis and reviews the potential promise of chelation therapy as a treatment for AD.