Istituto di Biofisica at Palermo, CNR, Palermo, Italy.
J Phys Condens Matter. 2012 Jun 20;24(24):244103. doi: 10.1088/0953-8984/24/24/244103. Epub 2012 May 18.
Recognizing the complexity of the fibrillogenesis process provides a solid ground for the development of therapeutic strategies aimed at preventing or inhibiting protein-protein aggregation. Under this perspective, it is meaningful to identify the possible aggregation pathways and their relative products. We found that Aβ-peptide dissolved in a pH 7.4 solution at small peptide concentration and low ionic strength forms globular aggregates without typical amyloid β-conformation. ThT binding kinetics was used to monitor aggregate formation. Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering were used for structural and morphological characterization of the aggregates. They appear stable or at least metastable with respect to fiber growth, therefore appearing as an incidental product in the pathway of fibrillogenesis.
认识到纤维形成过程的复杂性为开发旨在预防或抑制蛋白质-蛋白质聚集的治疗策略提供了坚实的基础。从这个角度来看，确定可能的聚集途径及其相对产物是有意义的。我们发现，在小肽浓度和低离子强度下，溶解在 pH 7.4 溶液中的 Aβ 肽形成无典型淀粉样 β 构象的球状聚集物。ThT 结合动力学用于监测聚集物的形成。圆二色性光谱、原子力显微镜成像、静态和动态光散射用于聚集物的结构和形态表征。它们相对于纤维生长是稳定的或至少是亚稳定的，因此在纤维形成途径中表现为偶然产物。
