脑内β淀粉样蛋白水平的调节

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (6): 711-714.

脑内β淀粉样蛋白水平的调节

王颖玉, 吴晶, 洪浩, 季晖, 吴玉林

中国药科大学药理教研室, 南京 230009, 江苏

收稿日期:2009-02-09 修回日期:2009-04-26 出版日期:2009-06-26 发布日期:2020-10-27
通讯作者: 洪浩, 男, 副教授, 研究方向:神经与内分泌药理。Tel:025-83207491 E-mail:haohongchina@hotmail.com
作者简介:王颖玉,女,硕士研究生,研究方向:神经与内分泌药理。

Regulation of β amyloid protein level in the brain

WANG Ying-yu, WU Jing, HONG Hao, JI Hui, WU Yu-lin

Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2009-02-09 Revised:2009-04-26 Online:2009-06-26 Published:2020-10-27

摘要/Abstract

摘要： β淀粉样蛋白(β amyloid 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。

关键词: β分泌酶, γ分泌酶, 脑啡肽酶, 胰岛素降解酶, 高级糖基化终产物受体(RAGE), 低密度脂蛋白受体相关蛋白1(LRP1)

Abstract: β amyloid protein (Aβ) including Aβ₄₀ and Aβ₄₂ are the important bioactive 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 eff lux 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 physiological condition and the reducing strategies on the level of brain Aβ under the pathological condition for developing new drugs in the treatment of AD.

Key words: β secretase, γsecretase, neprilysin, insulin-degrading enzyme, receptor for advanced end glycation products (RAGE), low-density lipoprotein receptor related protein 1 (LRP1)

中图分类号:

R338

王颖玉, 吴晶, 洪浩, 季晖, 吴玉林. 脑内β淀粉样蛋白水平的调节[J]. 中国临床药理学与治疗学, 2009, 14(6): 711-714.

WANG Ying-yu, WU Jing, HONG Hao, JI Hui, WU Yu-lin. Regulation of β amyloid protein level in the brain[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(6): 711-714.

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