Laboratory of Amyloid Biology, St. Petersburg State University, St. Petersburg 199034, Russia.
Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg 199034, Russia.
Int J Mol Sci. 2023 Sep 15;24(18):14122. doi: 10.3390/ijms241814122.
Numerous studies have demonstrated that people with type 2 diabetes mellitus (associated with IAPP peptide aggregation) show an increased incidence of Alzheimer's disease (associated with Aβ aggregation), but the mechanism responsible for this correlation is presently unknown. Here, we applied a yeast-based model to study the interactions of IAPP with PrP (associated with TSEs) and with the Aβ42 peptide. We demonstrated that fluorescently tagged IAPP forms detergent-resistant aggregates in yeast cells. Using the FRET approach, we showed that IAPP and Aβ aggregates co-localize and physically interact in yeast cells. We also showed that this interaction is specific and that there is no interaction between IAPP and PrP in the yeast system. Our data confirmed a direct physical interaction between IAPP and Aβ42 aggregates in a living cell. Based on these findings, we hypothesize that this interaction may play a crucial role in seeding Aβ42 aggregation in T2DM patients, thereby promoting the development of AD.
许多研究表明，2 型糖尿病患者（与 IAPP 肽聚集有关）阿尔茨海默病的发病率增加（与 Aβ 聚集有关），但目前尚不清楚导致这种相关性的机制。在这里，我们应用酵母模型来研究 IAPP 与 PrP（与 TSE 有关）和 Aβ42 肽的相互作用。我们证明了荧光标记的 IAPP 在酵母细胞中形成去污剂抗性聚集体。使用 FRET 方法，我们表明 IAPP 和 Aβ 聚集体在酵母细胞中共定位并发生物理相互作用。我们还表明，这种相互作用是特异性的，并且在酵母系统中 IAPP 和 PrP 之间没有相互作用。我们的数据证实了在活细胞中 IAPP 和 Aβ42 聚集体之间的直接物理相互作用。基于这些发现，我们假设这种相互作用可能在 2 型糖尿病患者中 Aβ42 聚集的形成中起关键作用，从而促进 AD 的发展。
