阿尔茨海默症病理机制中的金属代谢和金属药物

发布时间：2019-07-12 14:33

【摘要】：随着人口老龄化进程的发展,阿尔茨海默症(AD)已成为威胁中国和世界人口健康和经济的重大疾病.本文综述了近年来AD病理的分子机制的新进展,分析了其中金属代谢的意义.研究发现,在AD进程中,围绕淀粉样斑块(AP)和神经缠绕斑(NFT)的形成,多因素相互联系并发挥作用,这些主要因素包括金属内稳态、胰岛素抵抗、神经炎症、线粒体和血脑屏障改变等.与AD病理过程密切相关的主要蛋白质均参与了金属元素的生理代谢过程,而细胞金属离子的内稳态失衡加剧了AD病理的恶化.金属药物在AD诊断和治疗中可能具有以下的发展潜力:(1)AD早期诊断探针;(2)调节金属内稳态的配体和/或微量元素补充;(3)抗糖尿病金属配合物;(4)神经元和血脑屏障(BBB)保护金属药物.
[Abstract]:With the development of population aging, Alzheimer's disease (AD) has become a major disease threatening the health and economy of population in China and the world. In this paper, the new progress in the molecular mechanism of AD pathology in recent years is reviewed, and the significance of metal metabolism is analyzed. It is found that in the process of AD, many factors are related to each other and play an important role in the formation of (AP) and (NFT) in nerve wound plaques. These main factors include metal homeostasis, insulin resistance, neuroinflammation, changes in mitochondria and blood-brain barrier, and so on. The main proteins closely related to the pathological process of AD are involved in the physiological metabolism of metal elements, and the homeostasis imbalance of metal ions aggravates the deterioration of AD pathology. Metal drugs may have the following development potential in the diagnosis and treatment of AD: (1) AD early diagnostic probe; (2) ligands and / or trace elements supplement to regulate metal homeostasis; (3) antidiabetic metal complexes; (4) neuron and blood-brain barrier (BBB) to protect metal drugs.
【作者单位】：天然和仿生药物国家重点实验室;北京大学医学部药学院化学生物学系;
【基金】：国家自然科学基金(20971008,21271012) 教育部博士点基金方正创新药物基金资助天然和仿生国家重点实验室有组织项目支持
【分类号】：R749.16

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