关键词: Alzheimer’s disease Aβ membrane binding Aβ42 Langmuir balance cholesterol ganglioside isothermal calorimetry sphingomyelin β-amyloid

Mesh : Amyloid beta-Peptides / metabolism chemistry Humans Lipid Bilayers / metabolism chemistry Membrane Lipids / metabolism chemistry Protein Binding Cell Membrane / metabolism Alzheimer Disease / metabolism Animals Biophysical Phenomena Molecular Dynamics Simulation

来  源:   DOI:10.3390/ijms25126401   PDF(Pubmed)

Abstract:
Aβ peptides are known to bind neural plasma membranes in a process leading to the deposit of Aβ-enriched plaques. These extracellular structures are characteristic of Alzheimer\'s disease, the major cause of late-age dementia. The mechanisms of Aβ plaque formation and deposition are far from being understood. A vast number of studies in the literature describe the efforts to analyze those mechanisms using a variety of tools. The present review focuses on biophysical studies mostly carried out with model membranes or with computational tools. This review starts by describing basic physical aspects of lipid phases and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of the biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The Methodological Section is followed by the core of the review, which includes a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort to understand Aβ-bilayer binding. Concepts such as Aβ peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aβ-membrane interaction are separately identified and discussed.
摘要:
已知Aβ肽在导致富含Aβ的斑块沉积的过程中结合神经质膜。这些细胞外结构是阿尔茨海默病的特征,晚期痴呆的主要原因.Aβ菌斑形成和沉积的机制尚不清楚。文献中的大量研究描述了使用各种工具分析这些机制的努力。本综述侧重于主要使用模型膜或计算工具进行的生物物理研究。这篇综述首先描述了脂质相和常用模型膜(单层和双层)的基本物理方面。接下来是对应用于这些系统的生物物理技术的讨论,主要但不限于Langmuir单层,等温量热法,密度梯度超速离心,和分子动力学。方法部分之后是审查的核心,其中包括使用每种技术获得的重要结果的摘要。最后一部分致力于整体反思和理解Aβ-双层结合的努力。如Aβ肽膜结合的概念,吸附,和插入被定义和区分。膜脂序的作用,纳米域的形成,分别鉴定和讨论了Aβ膜相互作用中的静电力。
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