DNP enhanced ssNMR of amyloid-beta precursors and fibrils

阿尔茨海默病是一种神经退行性疾病，与大脑中的高淀粉样蛋白-β浓度密切相关。固态核磁共振（ssNMR）是一种广泛用于阐明淀粉样β蛋白形成的结构的方法。淀粉样蛋白-β前体结构的结构以及结合形成斑块的原纤维可以提供关于由淀粉样蛋白-β引起的破坏机制的线索。我的项目最初将探索淀粉样蛋白β和脂质分子之间的相互作用，这些分子类似于使用ssNMR在细胞膜中发现的分子。这将揭示蛋白质的构象，因为它与磷脂分子相互作用，条件保持尽可能的生理。该实验将用动态核极化（DNP）重复，动态核极化已被证明显著增加ssNMR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，以监测更真实生理条件下的淀粉样蛋白-β构象。在这些条件下，淀粉样β蛋白的分子相互作用将提供线索，作为蛋白质导致大脑细胞死亡的机制。

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.