Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders.
Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders.
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DOI：
10.2174/156720512799015064
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发表时间：
2012-01
影响因子：
2.1
通讯作者：
Martin B
中科院分区：
文献类型：
--
作者：
Cai H;Cong WN;Ji S;Rothman S;Maudsley S;Martin B
阿尔茨海默病和其他相关的神经退行性疾病是高度衰弱的疾病，影响着全球数百万人。为这些疾病开发有效治疗方法的努力充其量显示出有限的效果，到目前为止还没有真正的治疗方法。最近的临床和实验工作表明，许多神经退行性疾病经常表现出并存的代谢功能障碍，这可能会加剧神经症状。因此，代谢途径本身可能包含治疗主要神经退行性疾病的有希望的靶点，这是合理的。在这篇综述中，我们概述了阿尔茨海默病、亨廷顿病和帕金森病中代谢紊乱的一些最新证据，并讨论了代谢紊乱与神经系统退变病因之间潜在关系的几个潜在机制。我们还重点介绍了一些涉及外周代谢和中枢神经系统之间联系的重要信号通路，这些通路是未来治疗的潜在靶点，我们将回顾这一领域的一些临床进展。很可能在不久的将来，与多效性较差的药物相比，具有神经保护和‘全代谢’活性的组合疗法可能具有更好的疗效。
Alzheimer’s disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and ‘eumetabolic’ activities may possess superior efficacies compared to less pluripotent remedies.