Laboratory for Structure and Function of Biological Membranes, Faculté des Sciences, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, CP 206/2, Blvd. du Triomphe 1050, Brussels, Belgium.
Cell Mol Life Sci. 2011 Apr;68(8):1429-38. doi: 10.1007/s00018-010-0529-x. Epub 2010 Sep 19.
Alzheimer's disease (AD) is a neurodegenerative disorder occurring in the elderly. It is widely accepted that the amyloid beta peptide (Aβ) aggregation and especially the oligomeric states rather than fibrils are involved in AD onset. We used infrared spectroscopy to provide structural information on the entire aggregation pathway of Aβ(1-40), starting from monomeric Aβ to the end of the process, fibrils. Our structural study suggests that conversion of oligomers into fibrils results from a transition from antiparallel to parallel β-sheet. These structural changes are described in terms of H-bonding rupture/formation, β-strands reorientation and β-sheet elongation. As antiparallel β-sheet structure is also observed for other amyloidogenic proteins forming oligomers, reorganization of the β-sheet implicating a reorientation of β-strands could be a generic mechanism determining the kinetics of protein misfolding. Elucidation of the process driving aggregation, including structural transitions, could be essential in a search for therapies inhibiting aggregation or disrupting aggregates.
阿尔茨海默病（AD）是一种发生在老年人中的神经退行性疾病。人们普遍认为，β淀粉样肽（Aβ）的聚集，特别是寡聚体状态，而不是纤维，与 AD 的发病有关。我们使用红外光谱法提供了 Aβ（1-40）整个聚集途径的结构信息，从单体 Aβ到纤维的最终状态。我们的结构研究表明，寡聚物向纤维的转化是由反平行β-折叠向平行β-折叠的转变引起的。这些结构变化可以用氢键的断裂/形成、β-链的重新取向和β-片层的延伸来描述。由于其他形成寡聚体的淀粉样蛋白也观察到了反平行β-片层结构，β-片层的重组涉及β-链的重排可能是决定蛋白质错误折叠动力学的通用机制。阐明包括结构转变在内的聚集驱动过程对于寻找抑制聚集或破坏聚集的治疗方法可能至关重要。
