脑内β淀粉样蛋白水平的调节

Regulation of β amyloid protein level in the brain

β淀粉样蛋白(βamyloid protein,Aβ)是体内重要生物活性物质,主要包括Aβ40和Aβ42,它们在体内的利与害取决于其浓度高低。生理条件下脑内Aβ通过两个平衡维持在一定水平上,第一个平衡是Aβ的生成和降解,β分泌酶和γ分泌酶参与Aβ的生成,而脑啡肽酶和胰岛素降解酶参与Aβ的降解;第二个平衡是Aβ跨越血脑屏障的内向转运和外向转运,高级糖基化终产物受体(RAGE)是血脑屏障上Aβ内向转运体,而低密度脂蛋白受体相关蛋白1(LRP1)是血脑屏障上Aβ外向转运体。如果这两个平衡任何一个被破坏,将会导致脑内Aβ水平异常升高,继而Aβ聚集和沉淀,形成老年斑。本文综述生理条件下脑内Aβ水平的调节以及降低病理状态下脑内Aβ水平的策略。

β amyloid protein （Aβ） including Aβ40 and Aβ42 are the important bioaetive substances in vivo. Their toxic and beneficial attributes in the body depend on its concentration. The brain Aβ level is maintained by two balances under the physiological condition. The first balance is the generation involved in β- secretase and γ-secretase and the degradation involved in neprilysin （NEP） and insulin-degrading enzyme （IDE） of Aβ. The second one is the balance between the receptor for advanced end glycation products （ RAGE ）-mediated influx and low-density lipoprotein receptor related protein 1 （LRP1）-mediated efflux of Aβ across the blood-brain barrier （BBB）. Breakdowning any one of the two balances would result in the aggregation and precipitation of Aβ in the brain, which is a crucial event in the pathogenesis of Alzheimer＇ s disease （AD）. This paper reviews the regulation of brain Aβ level under the physiolocal condition and the reducing strategies on the level of brain Aβ under the pathological condition for developing new drugs in the treatment of AD.