Department of Chemical Sciences, University of Catania, I-95125, Catania, Italy; PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125, Catania, Italy.
Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, I-95126, Catania, Italy.
Arch Biochem Biophys. 2022 Oct 15;728:109354. doi: 10.1016/j.abb.2022.109354. Epub 2022 Jul 19.
Dipyridamole is currently used as a medication that inhibits blood clot formation and it is also investigated in the context of neurodegenerative and other amyloid related diseases. Here, we propose this molecule as a new diagnostic tool to follow the aggregation properties of three different amyloidogenic proteins tested (insulin, amylin and amyloid β peptide 1-40). Results show that dipyridamole is sensitive to early stage amyloid formation undetected by thioflavin T, giving a different response for the aggregation of the three different proteins. In addition, we show that dipyridamole is also able to enhance ubiquitin chain growth, paving the way to its potential application as therapeutic agent in neurodegenerative diseases.
双嘧达莫目前被用作抑制血栓形成的药物，也在神经退行性疾病和其他淀粉样相关疾病的研究中进行了研究。在这里，我们提出该分子作为一种新的诊断工具来跟踪三种不同的淀粉样蛋白（胰岛素、淀粉样肽 1-40 和淀粉样蛋白 β 肽 1-40）的聚集特性。结果表明，双嘧达莫对噻唑啉 T 无法检测到的早期淀粉样形成敏感，对三种不同蛋白质的聚集反应不同。此外，我们还表明，双嘧达莫还能够增强泛素链的生长，为其在神经退行性疾病中的潜在治疗应用铺平了道路。
