Metal chelators coupled with nanoparticles as potential therapeutic agents for Alzheimer's disease.
Metal chelators coupled with nanoparticles as potential therapeutic agents for Alzheimer's disease.
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DOI：
10.1166/jns.2009.005
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发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
Smith MA
中科院分区：
文献类型：
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作者：
Liu G;Men P;Perry G;Smith MA
阿尔茨海默病（Alzheimer's disease，AD）是一种严重的神经退行性疾病，其特征是记忆力的进行性和不可逆的丧失，随后出现完全性痴呆。尽管这种疾病的高患病率和巨大的经济和社会负担，一个解释性的病因或可行的治疗是不可用的。为了更好地了解该病的发病机制，并开发更有效的治疗药物，已经做出了很大的努力。然而，血脑屏障的存在极大地阻碍了成功，血脑屏障限制了大量潜在的治疗药物进入大脑。纳米颗粒介导的药物递送是克服这一障碍的少数有价值的工具之一，其作为潜在的AD治疗的应用显示出希望。在这篇综述中，目前的研究对纳米颗粒的螯合剂作为可能的治疗AD进行了讨论，因为几种金属被发现在AD大脑中过量，并可能在疾病的发展中发挥作用。具体而言，一种新的方法，涉及运输铁螯合剂进出大脑的纳米粒子被强调。这种方法可以提供一种更安全，更有效的方法，同时减少AD大脑中的几种有毒金属。它还可以提供对AD病理生理学机制的见解，并证明可用于治疗其他铁相关的神经退行性疾病，如弗里德赖希共济失调、帕金森病、亨廷顿病和Hallervorden-Spatz综合征。重要的是要注意，使用纳米颗粒介导的运输来促进有毒物质从体内患病部位排泄可能会推进纳米颗粒技术，该技术目前专注于疾病预防和治疗的靶向药物递送。纳米颗粒介导的药物转运在AD治疗中的应用处于非常早期的发展阶段，因此，需要进行更多的研究。
Alzheimer's disease (AD) is a devastating neuro-degenerative disorder characterized by the progressive and irreversible loss of memory followed by complete dementia. Despite the disease's high prevalence and great economic and social burden, an explicative etiology or viable cure is not available. Great effort has been made to better understand the disease's pathogenesis, and to develop more effective therapeutic agents. However, success is greatly hampered by the presence of the blood-brain barrier that limits a large number of potential therapeutics from entering the brain. Nanoparticle-mediated drug delivery is one of the few valuable tools for overcoming this impediment and its application as a potential AD treatment shows promise. In this review, the current studies on nanoparticle delivery of chelation agents as possible therapeutics for AD are discussed because several metals are found excessive in the AD brain and may play a role in the disease development. Specifically, a novel approach involving transport of iron chelation agents into and out of the brain by nanoparticles is highlighted. This approach may provide a safer and more effective means of simultaneously reducing several toxic metals in the AD brain. It may also provide insights into the mechanisms of AD pathophysiology, and prove useful in treating other iron-associated neurodegenerative diseases such as Friedreich's ataxia, Parkinson's disease, Huntington's disease and Hallervorden-Spatz Syndrome. It is important to note that the use of nanoparticle-mediated transport to facilitate toxicant excretion from diseased sites in the body may advance nanoparticle technology, which is currently focused on targeted drug delivery for disease prevention and treatment. The application of nanoparticle-mediated drug transport in the treatment of AD is at its very early stages of development and, therefore, more studies are warranted.