Global Center for Medical Engineering and Informatics, Osaka University, 2-1 Yamadaoka, Suita 565-0871, Japan.
Graduate School of Human and Environmental Studies, Kyoto University, Kyoto Sakyo-ku, Kyoto 606-8316, Japan.
Molecules. 2022 Jul 19;27(14):4588. doi: 10.3390/molecules27144588.
The supersaturation of a solution refers to a non-equilibrium phase in which the solution is trapped in a soluble state, even though the solute's concentration is greater than its thermodynamic solubility. Upon breaking supersaturation, crystals form and the concentration of the solute decreases to its thermodynamic solubility. Soon after the discovery of the prion phenomena, it was recognized that prion disease transmission and propagation share some similarities with the process of crystallization. Subsequent studies exploring the structural and functional association between amyloid fibrils and amyloidoses solidified this paradigm. However, recent studies have not necessarily focused on supersaturation, possibly because of marked advancements in structural studies clarifying the atomic structures of amyloid fibrils. On the other hand, there is increasing evidence that supersaturation plays a critical role in the formation of amyloid fibrils and the onset of amyloidosis. Here, we review the recent evidence that supersaturation plays a role in linking unfolding/folding and amyloid fibril formation. We also introduce the HANABI (HANdai Amyloid Burst Inducer) system, which enables high-throughput analysis of amyloid fibril formation by the ultrasonication-triggered breakdown of supersaturation. In addition to structural studies, studies based on solubility and supersaturation are essential both to developing a comprehensive understanding of amyloid fibrils and their roles in amyloidosis, and to developing therapeutic strategies.
溶液的过饱和度是指一种非平衡相，其中溶液被困在可溶解状态，即使溶质的浓度大于其热力学溶解度。过饱和度一旦被打破，就会形成晶体，溶质的浓度降低到其热力学溶解度。朊病毒现象被发现后不久，人们就认识到朊病毒疾病的传播和传播与结晶过程有一些相似之处。随后的研究探索了淀粉样纤维和淀粉样变性之间的结构和功能联系，进一步证实了这一观点。然而，最近的研究不一定集中在过饱和度上，这可能是因为结构研究取得了显著进展，阐明了淀粉样纤维的原子结构。另一方面，越来越多的证据表明，过饱和度在淀粉样纤维的形成和淀粉样变性的发生中起着关键作用。在这里，我们回顾了最近的证据，证明过饱和度在连接展开/折叠和淀粉样纤维形成中起着作用。我们还介绍了 HANABI（现代淀粉样纤维突发诱导剂）系统，该系统通过超声触发过饱和度的破坏，实现了淀粉样纤维形成的高通量分析。除了结构研究，基于溶解度和过饱和度的研究对于全面理解淀粉样纤维及其在淀粉样变性中的作用以及开发治疗策略都是至关重要的。
