淀粉样蛋白-β单体扩散受限条件下老年斑发展的数值建模

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Andrey V. Kuznetsov
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引用次数: 0

摘要

本文介绍了一种模拟老年斑进展的新模型,重点是淀粉样β(Aβ)单体和聚集体的浓度在不同神经元之间变化的情况。这些浓度的细胞外变化可能是由于 Aβ 单体的扩散率有限,以及脂膜上 Aβ 单体的生成率很高,因此 Aβ 单体的扩散驱动运输需要很大的浓度梯度。本文介绍了该模型的无量纲表述,确定了四个关键的无量纲参数,这些参数控制着 Aβ 单体和聚集体浓度的解,以及控制体积内不断增长的 Aβ 斑块的半径。这些参数包括 Aβ 单体的无量纲扩散率、Aβ 单体生成的无量纲速率以及 Aβ 单体和聚集体的无量纲半衰期。然后引入一个无量纲参数来评估叠加电容近似的有效性。针对 Aβ 单体扩散率大和蛋白质降解机制失灵导致 Aβ 单体和聚集体半衰期无限长的情况,得出了近似解。在这种情况下,Aβ 聚集体的浓度和 Aβ 斑块的半径只取决于一个表征 Aβ 单体产生速率的无量纲参数。根据近似解,Aβ 聚集体的浓度与单体生成速率成线性关系,Aβ 斑块的半径与单体生成速率的立方根成正比。然而,当偏离近似解的条件(如有限半衰期)时,Aβ 单体和聚集体的浓度以及斑块半径与所有四个无量纲参数呈现出复杂的依赖关系。例如,在生理半衰期条件下,斑块半径会达到一个最大值,然后趋于稳定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Numerical modeling of senile plaque development under conditions of limited diffusivity of amyloid-β monomers

Numerical modeling of senile plaque development under conditions of limited diffusivity of amyloid-β monomers

This paper introduces a new model to simulate the progression of senile plaques, focusing on scenarios where concentrations of amyloid beta (Aβ) monomers and aggregates vary between neurons. Extracellular variations in these concentrations may arise due to limited diffusivity of Aβ monomers and a high rate of Aβ monomer production at lipid membranes, requiring a substantial concentration gradient for diffusion-driven transport of Aβ monomers. The dimensionless formulation of the model is presented, which identifies four key dimensionless parameters governing the solutions for Aβ monomer and aggregate concentrations, as well as the radius of a growing Aβ plaque within the control volume. These parameters include the dimensionless diffusivity of Aβ monomers, the dimensionless rate of Aβ monomer production, and the dimensionless half-lives of Aβ monomers and aggregates. A dimensionless parameter is then introduced to evaluate the validity of the lumped capacitance approximation. An approximate solution is derived for the scenario involving large diffusivity of Aβ monomers and dysfunctional protein degradation machinery, resulting in infinitely long half-lives for Aβ monomers and aggregates. In this scenario, the concentrations of Aβ aggregates and the radius of the Aβ plaque depend solely on a single dimensionless parameter that characterizes the rate of Aβ monomer production. According to the approximate solution, the concentration of Aβ aggregates is linearly dependent on the rate of monomer production, and the radius of an Aβ plaque is directly proportional to the cube root of the rate of monomer production. However, when departing from the conditions of the approximate solution (e.g., finite half-lives), the concentrations of Aβ monomers and aggregates, along with the plaque radius, exhibit complex dependencies on all four dimensionless parameters. For instance, under physiological half-life conditions, the plaque radius reaches a maximum value and stabilizes thereafter.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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