Is RAGE still a therapeutic target for Alzheimer's disease?
Is RAGE still a therapeutic target for Alzheimer's disease?
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DOI：
10.4155/fmc.12.51
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发表时间：
2012-05
影响因子：
4.2
通讯作者：
Deane RJ
中科院分区：
文献类型：
--
作者：
Deane RJ
晚期糖基化终末产物受体（receptor for advanced glycation end products，AGEs）是一种多配体受体，参与炎症性疾病、肿瘤生长、糖尿病并发症和阿尔茨海默病（Alzheimer's disease，AD）。β-淀粉样蛋白通过血脑屏障（BBB）将循环中的β-淀粉样蛋白毒素转运到大脑中。RAGE-淀粉样蛋白-β毒素在BBB处的相互作用导致氧化应激、炎症反应和脑血流量减少。因此，调节BBB处和/或脑内的α-淀粉酶活性可能对AD患者有益。在此，RAGE-配体相互作用的结构-功能关系和作用的AD和其他RAGE相关疾病的治疗的发展中的潜在目标的RAGE的作用进行了讨论。尽管最近在开发基于RAGE的AD疗法方面遇到了挫折，但新一代调节AD活性的化合物可能是有效的。在临床试验之前，需要在AD的啮齿动物和非啮齿动物模型中仔细研究新一代AD拮抗剂，以确保长期治疗的安全性和有效性。
The receptor for advanced glycation end products (RAGE) is a multiligand receptor involved in inflammatory disorders, tumor outgrowth, diabetic complications and Alzheimer's disease (AD). RAGE transports circulating amyloid-β toxins across the blood–brain barrier (BBB) into the brain. RAGE–amyloid-β toxin interaction at the BBB leads to oxidative stress, inflammatory responses and reduced cerebral blood flow. Thus, regulating RAGE activity at the BBB and/or within brain could be beneficial to AD patients. Herein, the structure–function relation for RAGE–ligand interaction and the role of RAGE as a potential target in the development of treatments for AD and other RAGE-associated disorders are discussed. Despite recent setbacks in the development of RAGE-based therapies for AD, a new generation of compounds that regulate RAGE activity could be efficacious. Careful studies are needed in rodent and nonrodent animal models of AD with new the generation of RAGE antagonists to ensure safety and efficacy in chronic treatment before clinical trials.