Receptor for advanced glycation end products: its role in Alzheimer's disease and other neurological diseases.
Receptor for advanced glycation end products: its role in Alzheimer's disease and other neurological diseases.
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DOI：
10.2217/14796708.4.2.167
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发表时间：
2009
期刊：
影响因子：
1.3
通讯作者：
Sabbagh M
中科院分区：
文献类型：
--
作者：
Lue LF;Walker DG;Jacobson S;Sabbagh M
晚期糖基化终产物受体（RAGE）已被证明在越来越多的重要神经系统疾病的致病机制中发挥核心作用，包括阿尔茨海默病（AD）和中风。两种功能类型的RAGE与神经系统疾病相关：细胞膜结合型（全长）和可溶性。一般来说，配体结合全长RAGE启动持续的细胞激活和受体依赖的信号传导，导致炎症和细胞应激，并最终与RAGE表达增加有关。相比之下，通过选择性剪接或蛋白质水解产生的可溶形式的RAGE可以通过阻止配体与全长RAGE结合来降低配体与膜RAGE相互作用的严重程度。这可以抑制疾病状态中涉及的神经毒性或促炎反应。本文综述了RAGE的病理生物学，重点介绍了RAGE的可溶性形式，并讨论了其与AD和其他神经系统疾病的相关性，以及如何操纵不同形式的RAGE成为一种强有力的治疗策略。
The receptor for advanced glycation end products (RAGE) has been demonstrated to play a central role in the pathogenic mechanisms of a growing number of important neurological diseases, including Alzheimer’s disease (AD) and stroke. Two functional types of RAGE have been associated with neurological diseases: cell membrane-bound (full length) and soluble. In general, ligand binding to full-length RAGE initiates sustained cellular activation and receptor-dependent signaling resulting in inflammation and cellular stress, and is ultimately associated with increased RAGE expression. By comparison, soluble forms of RAGE, generated either by alternative splicing or by proteolysis, can reduce the severity of the consequence of ligand-membrane RAGE interactions by preventing ligands from binding to the full-length RAGE. This can inhibit the neurotoxic or proinflammatory responses involved in disease states. This article reviews the pathobiology of RAGE, with emphasis on soluble forms of RAGE, and discusses its relevance to AD and to other neurological diseases, as well as how manipulation of the different forms of RAGE is becoming a powerful therapeutic strategy.