淀粉样蛋白组装过程中碎片化作用的鉴定及其优化应用

M. Chyba, J. Coron, Pierre Gabriel, Yuriy Mileyko, H. Rezaei
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引用次数: 1

摘要

目标是建立一个淀粉样蛋白形成的动力学模型,该模型将考虑到碎片对模板界面从头创建的贡献。我们提出了一个新的,更全面的数学模型,考虑到以前被忽视的现象可能发生在模板和破碎过程中。特别是,我们试图通过将相同长度的聚合物分离成几个隔室来捕获朊病毒折叠的拓扑结构和几何形状对给定长度的聚合物的伸长率和断裂性能的潜在影响。此外,我们将几何控制技术应用到新模型中,以设计加速当前扩增协议的最佳策略,例如蛋白质错误折叠循环扩增(PMCA)。目的是减少诊断许多神经退行性疾病所需的时间。在碎片优化的一般问题中,确定加速复制的最优策略仍然是一个悬而未决的问题。
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Identification of the Fragmentation Role in the Amyloid Assembling Processes and Application to their Optimization
The goal is to establish a kinetic model of amyloid formation which will take into account the contribution of fragmentation to the de novo creation of templating interfaces. We propose a new, more comprehensive mathematical model which takes into account previously neglected phenomena potentially occurring during the templating and fragmentation processes. In particular, we try to capture a potential effect of the topology and geometry of prion folding on the elongation and fragmentation properties of a polymer of a given length by separating polymers of the same length into several compartments. Additionally, we apply techniques from geometric control to the new model to design optimal strategies for accelerating the current amplification protocols, such as the Protein Misfolding Cyclic Amplification (PMCA). The objective is to reduce the time needed to diagnose many neurodegenerative diseases. Determining the optimal strategy for accelerated replication in the general problem of fragmentation optimization is still an open question.
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