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

疏水残基对 Aβ 淀粉样肽热力学和动力学的贡献

• 批准号: 9104398
• 负责人: Liliya Vugmeyster
• 金额: $ 30.42万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9104398
• 关键词: Contributions; Hydrophobic; Residues; into; Thermodynamics

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.

摘要：阿尔茨海默病的特征之一是存在神经毒性