DNP enhanced ssNMR of amyloid-beta precursors and fibrils

DNP 增强 β 淀粉样蛋白前体和原纤维的 ssNMR

• 批准号: 1794242
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1794242
• 关键词: DNP; enhanced; ssNMR; amyloid; beta

Alzheimer's disease is a neurodegenerative disorder that is strongly associated with high amyloid-beta concentration in the brain. A method that has been widely used to elucidate the structures formed by the amyloid-beta protein is solid-state nuclear magnetic resonance (ssNMR). The structures of amyloid-beta precursor structures as well as the fibrils which associate to form plaques may provide clues as to the mechanism of destruction caused by the amyloid-beta. My project will initially look to probe the interaction between amyloid-beta and lipid molecules that resemble those found in the membranes of cells using ssNMR. This will reveal the conformation of the protein as it interacts with the phospholipid molecules, with conditions being kept as physiological as possible. This experiment will be repeated with dynamic nuclear polarisation (DNP), which has been shown to significantly increase the signal intensity of ssNMR spectra. Depending on the results of these initial studies, membrane material will be taken from the brain of a mouse to monitor amyloid-beta conformation in more realistic physiological conditions. The molecular interactions of amyloid-beta under these conditions will provide clues as the mechanism by which the protein causes cell death in the brain.

阿尔茨海默病是一种神经退行性疾病，与大脑中高淀粉样蛋白浓度密切相关。固态核磁共振（ssNMR）已被广泛用于阐明淀粉样蛋白形成的结构。淀粉样蛋白前体结构的结构以及与形成斑块相关的原纤维的结构可能为淀粉样蛋白引起的破坏机制提供线索。我的项目最初将利用ssNMR探索淀粉样蛋白- β和脂质分子之间的相互作用，这些分子与细胞膜上发现的分子相似。这将揭示蛋白质与磷脂分子相互作用时的构象，并尽可能保持生理条件。这个实验将在动态核极化（DNP）中重复，这已经被证明可以显著增加ssNMR光谱的信号强度。根据这些初步研究的结果，将从小鼠大脑中提取膜材料，以在更现实的生理条件下监测淀粉样蛋白的构象。淀粉样蛋白- β在这些条件下的分子相互作用将为蛋白质导致大脑细胞死亡的机制提供线索。