Aβ的外周清除与阿尔茨海默病  

Peripherocial Clearance of Amyloid-Beta in Alzheimer's Disease

作　　者：张云莎[1] 郭茂娟[1] 李虎虎[1] 姜希娟[1] 杜欢[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》2016年第22期4398-4400,4338,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年基金项目(81303088);高等学校博士学科点专项科研基金项目(20131210120004);天津市高等学校科技发展基金计划项目(20130213)

摘　　要：脑β-淀粉样蛋白(Amyloid-β,Aβ)沉积是阿尔茨海默病(Alzheimer's disease,AD)发病的核心问题。Aβ的沉积与其生成和清除失衡有关,尤其是清除障碍是导致Aβ沉积的主要原因。Aβ经RAGE,LRP1及P-gp介导跨血脑屏障(blood-brain barrier,BBB)转运至外周和经血管旁淋巴引流途径到达局部淋巴结是脑Aβ转运至外周进而发挥外周清除效应的两条途径,亦是Aβ清除的主要途径。RAGE,LRP1及P-gp表达异常、血管旁淋巴引流途径受阻及外周清除组织功能障碍均会影响Aβ外周清除,促进AD病程的进展。因此干预BBB上转运体的功能及血管旁淋巴引流通路,实现外周组织的清除效应,有利于Aβ外周清除。随着外周Aβ清除,脑Aβ则会源源不断转运至外周,发挥外周降解效应,即外周Sink效应。基于外周Sink效应,将AD治疗重点由促进Aβ脑内清除转为外周清除将是一条有效且相对安全的途径。Aggregation and accumulation of amyloid-β peptide （Aβ） in brain tissues play pivotal and causal roles in the pathogenesis of AD and has since become the major therapeutic target for this disease. The cause of the accumulation of Aβ may be due to faulty clearance of Aβ from brain. Aβ transport across the blood -brain barrier （BBB） from brain to blood and perivascular drainage of Aβ to lymph nodes are the major pathways of Aβ clearance. Regulating RAGE, LRP-land P-gp, are the main transporters on the BBB, and maintaining the function of peripheral tissues can inprove Aβ peripheral clearance, hence to reduce brain Aβ. Considering the limitated delivery of drugs across the BBB and adverse effects of immuno-therapies targeting the central clearance of amyloid plaques, we propose that therapies to restore the peripheral Aβ ＇Sink＇ action, hold potential to reduce brain Aβ are effective and safe.

关 键 词：阿尔茨海默病 Β-淀粉样蛋白 外周清除 

分 类 号：R743.9[医药卫生—神经病学与精神病学] R749.16[医药卫生—临床医学]