Yang Chien-I, Tsai Brook N F, Huang Shing-Jong, Wang Ting-Yu, Tai Hwan-Ching, Chan Jerry C C
Department of Chemistry, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, 106, Taiwan.
Instrumentation Center, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, 106, Taiwan.
Chem Asian J. 2015 Sep;10(9):1967-71. doi: 10.1002/asia.201500482. Epub 2015 Jul 16.
One of the hallmarks of Alzheimers disease is the deposition of amyloid plaques, which consist of β-amyloid (Aβ) peptides in fibrillar states. Nonfibrillar Aβ aggregates have been considered as an important intermediate in the pathway of fibrillization, but little is known about the formation mechanism. The on-pathway β-sheet intermediates of Aβ40 peptides can be trapped by incubating the peptides in liposomes formed by zwitterionic lipids. The aggregates of Aβ40 peptides have been prepared at a peptide concentration of less than 10 μm. Solid-state NMR spectroscopy data show that the backbone conformation of the aggregates is almost identical to that of the fibrils formed in free solution. In contrast to anionic lipids, zwitterionic lipids, which are typical of neuronal soma, did not induce any significant conformational difference in Aβ40 fibrils. This liposome-Aβ system may serve as a useful model to study the fibril formation mechanism.
阿尔茨海默病的一个标志性特征是淀粉样斑块的沉积，其由处于纤维状态的β-淀粉样蛋白（Aβ）肽组成。非纤维状Aβ聚集体被认为是纤维化途径中的重要中间体，但对其形成机制知之甚少。通过将Aβ40肽在两性离子脂质形成的脂质体中孵育，可以捕获Aβ40肽的途径上的β-折叠中间体。已在小于10μm的肽浓度下制备了Aβ40肽的聚集体。固态核磁共振光谱数据表明，聚集体的主链构象与在游离溶液中形成的原纤维几乎相同。与阴离子脂质相反，作为神经元胞体典型特征的两性离子脂质不会在Aβ40原纤维中诱导任何显著的构象差异。这种脂质体-Aβ系统可作为研究原纤维形成机制的有用模型。
