RAGE与阿尔茨海默病关系的研究进展  

Research progress of Receptor for Advanced Glycation Endproducts in Alzheimer's Disease

作　　者：杜欢[1] 郭茂娟[1] 姜希娟[1] 王一婧[1] 胡先同[1] 

机构地区：[1]天津中医药大学,天津300193

出　　处：《现代生物医学进展》2014年第14期2773-2775,2793,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年基金项目(81303088)

摘　　要：阿尔茨海默病属于神经系统退行性疾病,该类疾病给社会和家庭带来了沉重的负担,且目前尚无一疗效突破性药物,已经成为一个严重的社会问题和经济问题。Aβ是阿尔茨海默病的重要发病机制之一,通过多种途径介导神经损伤,其中与细胞表面的结合位点结合而引发的病理损害成为当今的前沿认识。一方面,它们可以使Aβ聚集,造成细胞膜的直接损伤;另一方面,它们可以以受体的形式,参与细胞内的信号传导;另外,还可以激活细胞内吞作用,通过溶酶体途径造成细胞损伤。关于与Aβ结合的细胞表面结合位点,晚期糖基化终末产物受体备受瞩目。它是一种多功能受体,属于细胞表面免疫球蛋白家族成员,在神经元、小胶质细胞以及血管内皮细胞上都有表达,Aβ是它的配体之一。研究已证实,它与Aβ相互作用,通过激活细胞内不同的信号通路,对阿尔茨海默病的发生发展发挥重要作用。随着对它的不断深入研究,有望在防治退行性疾病方面产生新的治疗策略与措施。Alzheimer＇s disease belongs to neurodegenerative diseases, which has brought a heavy burden to society and family, and currently there is not effect medicine, so it has become a serious social and economic problem. It was shown Aβ as a key pathogenic entity in neuronal dysfunction and neuropathologic changes of Alzheimer＇s disease. Several mechanisms could potentially target Aβ to cellular element. In this regard, cell surface-binding sites are logical to consider for multiple reasons： for one thing, their capacity to concentrate Aβ at the plasma membrane, where it could directly damage membranes; for another thing, the possibility that they could function as receptors which engage in intracellular signaling mechanisms; and finally their ability to trigger endocytosis, potentially concentrating toxic species in the endolysosomal pathway where disruption of lysosomal integrity could induce severe cellular damage. We have focused our attention on Receptor for advanced glycation endproducts, a multiligand receptor in the immunoglobulin superfamily, binds a broad repertoire of ligands, including Aβ. In the CNS, it can be expressed on neurons, microglia, and endothelial cells. It was shown that the interaction of Aβ with receptor for advanced glycation endproducts can contribute to activate various cell signaling pathways in the pathogenesis of Alzheimer＇s disease. The review focuses on our current knowledge of receptor for advanced glycation endproducts pathways and new treatment strategies based on Alzheimer＇s disease.

关 键 词：阿尔茨海默病 晚期糖基化终末产物受体 研究进展 

分 类 号：R592[医药卫生—老年医学] R749.16[医药卫生—内科学]