Vestergaard Mun'delanji, Hamada Tsutomu, Takagi Masahiro
Japan Advanced Institute of Science and Technology, School of Materials Science, 1-1 Asahidai, Nomi City, Ishikawa 923-1292, Japan.
Biotechnol Bioeng. 2008 Mar 1;99(4):753-63. doi: 10.1002/bit.21731.
One of the major tasks in understanding the etiopathogenesis of amyloid beta-induced neurotoxicity of Alzheimer's disease (AD), is in fully capturing the large number of the biochemical processes that influence each other during the course of the disease, in vivo. Model membranes possess, as their main strength, the ability to enable the researcher to manipulate a 'biological' micro-vesicle under a controlled environment. This review narrowly focuses on discussing the exploitation of model membranes for improved understanding of some of the mechanisms governing AD's amyloid beta-induced neurotoxicity. Amyloid beta (Abeta) is cleaved from a membrane-located amyloid precursor protein by membrane-located enzymes. The relative spatial localization of the involved biomolecules within the membrane bilayer is crucial in influencing Abeta production, its aggregation on the membrane surface or insertion into the membrane, and fibril formation: all important processes in causing neurotoxicity. The lipid composition of the bilayer is similarly important. The review also attempts to highlight current and future challenges in using model membranes for studying biochemical processes.
理解阿尔茨海默病（AD）中β-淀粉样蛋白诱导神经毒性的发病机制的主要任务之一，是全面掌握在疾病过程中体内相互影响的大量生化过程。模型膜的主要优势在于，能够使研究人员在可控环境下操控一个“生物”微囊泡。本综述将重点讨论如何利用模型膜更好地理解一些控制AD中β-淀粉样蛋白诱导神经毒性的机制。β-淀粉样蛋白（Aβ）由膜定位酶从膜定位的淀粉样前体蛋白上切割而来。膜双层内相关生物分子的相对空间定位对于影响Aβ的产生、其在膜表面的聚集或插入膜内以及纤维形成至关重要：这些都是导致神经毒性的重要过程。双层膜的脂质组成同样重要。本综述还试图强调在使用模型膜研究生化过程方面当前和未来面临的挑战。
