Disturbed copper bioavailability in Alzheimer's disease.
Disturbed copper bioavailability in Alzheimer's disease.
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DOI：
10.4061/2011/345614
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发表时间：
2011
影响因子：
--
通讯作者：
Multhaup G
中科院分区：
文献类型：
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作者：
Kaden D;Bush AI;Danzeisen R;Bayer TA;Multhaup G
最近来自体外、动物和人体研究的数据揭示了铜在阿尔茨海默病许多方面的积极作用。铜促进了APP的非淀粉样变性过程，从而降低了细胞培养系统中Aβ的产生，并增加了APP转基因小鼠的寿命，减少了可溶性淀粉样蛋白的产生。在一项针对阿尔茨海默病患者的临床试验中，作为诊断标志物的脑脊液中a β水平的下降在verum组（8 mg铜/天）中有所减少，表明铜治疗的有益效果。这些观察结果与使用旨在使大脑中金属水平正常化的化合物（如PBT2）治疗的益处一致。本文回顾的数据表明，AD患者体内的金属平衡明显受到干扰。迫切需要更多的研究来了解如何在治疗上解决这种障碍。
Recent data from in vitro, animal, and human studies have shed new light on the positive roles of copper in many aspects of AD. Copper promotes the non-amyloidogenic processing of APP and thereby lowers the Aβ production in cell culture systems, and it increases lifetime and decreases soluble amyloid production in APP transgenic mice. In a clinical trial with Alzheimer patients, the decline of Aβ levels in CSF, which is a diagnostic marker, is diminished in the verum group (8 mg copper/day), indicating a beneficial effect of the copper treatment. These observations are in line with the benefit of treatment with compounds aimed at normalizing metal levels in the brain, such as PBT2. The data reviewed here demonstrate that there is an apparent disturbance in metal homeostasis in AD. More research is urgently needed to understand how this disturbance can be addressed therapeutically.