Brain membrane cholesterol domains, aging and amyloid beta-peptides.
Brain membrane cholesterol domains, aging and amyloid beta-peptides.
复制标题
脑膜胆固醇结构域、衰老和淀粉样β-肽。
DOI：
10.1016/s0197-4580(02)00018-0
复制
发表时间：
2002
影响因子：
4.2
通讯作者：
Chochina,SvetlanaV
中科院分区：
文献类型：
--
作者：
Wood,WGibson;Schroeder,Friedhelm;Igbavboa,Urule;Avdulov,NicolaiA;Chochina,SvetlanaV
脂质对膜的结构和功能完整性至关重要。膜脂不是随机分布的，而是分布在不同的结构域。这些结构域包括外表面和细胞表面小叶、胆固醇池、环状脂质和脂筏。膜脂结构域被认为参与多种不同的功能，包括信号转导、脂质转运和代谢以及细胞生长。脑膜脂结构域在不同实验条件、衰老和某些神经退行性疾病的作用下被改变。最近的数据显示，膜脂结构域可能是阿尔茨海默病的一个目标，这是非常有趣的可能性。越来越多的证据表明胆固醇与阿尔茨海默病之间存在关联，胆固醇是膜脂结构域的主要组成部分。在这里，我们讨论最近的数据在脑膜脂结构域强调胆固醇的结构和功能作用。此外，脂质结构域和衰老，以及脂质结构域和淀粉样β肽（a β）的潜在相互作用是阿尔茨海默病患者大脑中老年斑的主要组成部分。我们认为，与神经元质膜中总胆固醇或总胆固醇相比，年龄变化对胆固醇不对称分布的影响为a β在质膜中的积累提供了一个合作环境，而a β的积累部分是由于与膜外叶或外叶中的胆固醇直接的物理化学相互作用。
Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. These domains consist of the exofacial and cytofacial leaflets, cholesterol pools, annular lipids, and lipid rafts. Membrane lipid domains have been proposed to be involved in a variety of different functions including e.g. signal transduction, lipid transport and metabolism, and cell growth. Membrane lipid domains have been identified in brain and can be modified by different experimental conditions, aging and certain neurodegenerative diseases. Recent data reveal the very interesting possibility that membrane lipid domains may be a target of Alzheimer’s disease. There is a growing body of evidence showing an association between cholesterol and Alzheimer’s disease, and cholesterol is a major component of membrane lipid domains. Here we discuss recent data on brain membrane lipid domains emphasizing the structural and functional role of cholesterol. In addition, lipid domains and aging, and the potential interaction of lipid domains and amyloid beta-peptides (Aβ) that are a major component of senile plaques in brains of Alzheimer’s patients are considered. We propose that age changes in the asymmetric distribution of cholesterol in contrast to total or bulk cholesterol in neuronal plasma membranes provides a cooperative environment for accumulation of Aβ in plasma membranes and the accumulation of Aβ is due in part to a direct physico-chemical interaction with cholesterol in the membrane exofacial or outer leaflet.