Contributions of Hydrophobic Residues into the Thermodynamics and Kinetics of Amyloid Abeta Peptide

总结：阿尔茨海默病的特征之一是存在神经毒性 脑组织中的沉积物，主要由称为A肽的短肽组成。 阐明负责形成和稳定病理相关的 原纤维对于设计对抗该疾病的预防和治疗剂是重要的。我们的目标 为了研究作为整个原纤维的一部分的原纤维稳定化过程的一个特定方面 稳定性图片，即位于疏水性中的单个非极性侧链的作用 纤维的内部因此，我们的研究将补充全球对稳定性的调查， 揭示最重要的当地网站，然后可以成为设计的目标， 破坏原纤维稳定性的修饰、配体和突变体。我们的工具将允许 在选定的网站的动力学和热力学稳定的平衡视图。我们将研究 野生型肽的两种不同形态以及与早期 疾病的发作。我们将利用氘核磁共振光谱， 计算机模拟来实现这一目标。

Summary: One of the characteristics of Alzheimer's disease is the presence of neurotoxic deposits in brain tissues, which are largely made up of a short peptide referred to as A The elucidation of the factors responsible for the formation and stabilization of pathologically relevant fibrils is important for designing preventive and therapeutic agents to combat the disease. We aim to investigate one specific aspect of the fibril stabilization process as part of the overall fibril stability picture, namely the role of individual non-polar side chains located in the hydrophobic interior of the fibrils. Thus, our studies will complement global investigations into stability by revealing the most important local sites, which can then become targets for the design of modifications, ligands, and mutants that disrupt the stabilization of the fibrils. Our tools will allow for a balanced view of kinetic and thermodynamic stabilization at the selected sites. We will study two different morphologies of the wild-type peptide as well as a mutant associated with the early onset of the disease. We will utilize deuterium nuclear magnetic resonance spectroscopy and computational modeling to achieve this goal.