阿尔茨海默病与铁稳态失常及相关药物研发现状赵香玉王耀王贵彬.pdfVIP

尔茨海默病与铁稳态失常及相关药物研发现状 赵香玉, 王耀, 王贵彬, 张建军*1 ( 中国医学科学院、北京协和医学院药物研究所，新药作用机制与药效评价北京 市重点实验室, 北京 100050) 摘要: 铁是人体含量最多的金属元素，参与多种生理活动，对神经系统功能 的发挥也起着重要作用。正常状态下，铁稳态受到严格的调控，铁过量或不足均 会引发相应疾病。大量研究显示阿尔茨海默病 (Alzheimer s disease, AD) 患者机 体铁稳态失常并且铁稳态的失常与AD 标志性病理变化相关。虽然针对AD 与铁 稳态关系的研究很多，但目前铁在AD 发病中的确切地位尚不明确。本文将从生 理状态下铁稳态的维持、铁稳态异常在AD 发病中发挥的作用和以铁清除为靶点 的药物研发现状进行综述。 关键词: 阿尔茨海默病; 铁稳态; 氧化应激; 淀粉样蛋白; 载脂蛋白 E; 铁 清除剂 中图分类号: R966 文献标识码: A 文章编号: 0513-4870(2016) Disruption of iron homeostasis and relevant pharmacotherapies in Alzheimer s disease ZHAO Xiang-yu, WANG Yao, WANG Gui-bin, ZHANG Jian-jun* (Beijing Key Laboratory of New Drug Mechanisms and Pharmacological evaluation Study, Institute of Materia Medica , Chinese A cademy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China) Abstract: Iron is the most abundant metal element to support the bodys physiological activities and play crucial roles in the central nervous system. Iron homeostasis is under strict control in normal circumstances, and some diseases will occur once the homeostasis was disrupted. Numerous researches suggest that iron 收稿日期: 2016-03-15; 修回日期: 2016-04-13. 基金项目: 科技部国际合作项目 (2010DFB32900); 国家自然科学基金资助项目面上项目 . *通讯作者Tel/Fax:86-10 E-mail: jjzhan g@imm.ac.cn homeostasis disruptes in Alzheimer s disease (AD) and the homeostasis disruption interacts with AD s hallmarks. Dispute still exists on how iron plays a role in AD despite of the great number of researches. This article will focus on iron metabolism, normal function in the brain and recent therapies of AD based on iron chelation. Key words: Alzheimer s disease; iron homeostasis; oxidative stress; amyloid- ; apolipoprotein E; iron c