维甲酸受体激动剂AM80抗阿尔治海默症最新研究进展  

Advances of retinoic acid receptor agonist AM80 in Alzheimer's disease drug development

作　　者：乔爱敏 王宜海 程鹏 

机构地区：[1]广东药科大学生命科学与生物制药学院生物资源和创新药物研究中心,广东广州510006 [2]广东药科大学药学院广东省先导化合物与药物发现工程中心,广东广州510006

出　　处：《沈阳药科大学学报》2017年第11期1028-1032,共5页Journal of Shenyang Pharmaceutical University

基　　金：广东省自然科学基金(No.2016A030313732);广东省医学科学基金(No.A2015248)

摘　　要：目的综述AM80他米巴罗汀(tamibarotene,AM80)抗阿尔治海默症(Alzheimer's Disease,AD)药理作用及其作用机制、不良反应以及临床用药安全等最新研究进展。方法通过阅读近几年国内外的相关文献,对AM80抗阿尔治海默症最新研究报道进行详细的归纳总结。结果 AM80是一个合成的维甲酸受体激动剂,具有很好的抗阿尔治海默症作用。AM80作为一个多靶点药物,它通过转录调控多种与AD发病相关的基因;能够减少β淀粉样肽在脑部的沉积;还能够改善AD小鼠的学习记忆功能;有效弥补脑内乙酰胆碱的减少;并且能够增加小胶质细胞对Aβ(beta amyloid)的降解功能并伴随脑部炎症的减少。结论 AM80有望成为一个安全和有效的预防和治疗AD的药物,具有广泛的临床应用前景。Objective To summarize progress in the latest research of pharmacological effects,adverse effects and clinical safety of Tamibarotene（AM80） in the treatment of Alzheimer＇ s disease（AD）. Methods The latest researches about AM80 in Alzheimer＇s disease are summarized by reviewing the relevant literatures in the recent years at home and abroad. Results Tamibarotene（AM80）,a synthetic retinoid approved in Japan for treatment of acute promyelocytic leukemia（APL）, is a retinoic acid receptor（RAR） agonist and it is considered to be a promising candidate drug for treatment of AD because of its transcriptional controls of multiple target genes involved in etiology and pathology of AD. AM80 could reduce the A β deposit in the brain; improve the learning and memory function of AD mice; ameliorate the decrease of cortical acetylcholineand reduce secretion of proinflammatory cytokines as well as enhance the microgia cell degradating A β function. Conclusions AM80 is expected to be a safe and effective candidate for the prevention and treatment of Alzheimer＇s disease,with a wide range of clinical application prospects.

关 键 词：他米巴罗汀 阿尔治海默症 维甲酸受体 

分 类 号：R96[医药卫生—药理学]