Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung Chia-Yi 62102, Taiwan, ROC.
Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung Chia-Yi 62102, Taiwan, ROC; Center for Nano Bio-Detections, National Chung Cheng University, Min-Hsiung Chia-Yi 62102, Taiwan, ROC; Center for Innovative Research on Aging Society (CIRAS), National Chung Cheng University, Min-Hsiung Chia-Yi 62102, Taiwan, ROC.
Biomed Pharmacother. 2022 Jul;151:113177. doi: 10.1016/j.biopha.2022.113177. Epub 2022 May 27.
Amyloidoses are caused by the deposition of amyloid fibrils ascribed to protein misfolding. In this study, we examined the antiamyloidogenic and antioxidative activities of quercetin, a plant flavonol from the flavonoid group of polyphenols, on mouse prion protein (moPrP) with biophysical approaches. As the results show, quercetin binds to the C-terminal region of moPrP, and quercetin binding does not affect the structure of moPrP. However, quercetin binding accelerates moPrP fibrillation and changes the structure of moPrP fibrils. Unlike typical prion fibrils, quercetin-bound fibrils are sensitive to proteinase K and are loosely structured. Moreover, due to high antioxidant activity of flavonoid, quercetin-bound fibrils lack imbalance of free radicals and, therefore, they are nontoxic towards neuroblastoma cells. The quercetin shows its uniqueness from typical antiamyloidogenic drugs which either suppress the development of amyloid or eliminate formed amyloids. Quercetin binding converts moPrP into protease-sensitive and non-cytotoxic fibrils. This work provides a powerful resolution in the advancement of antiamyloidogenic treatment.
淀粉样变性是由淀粉样纤维的沉积引起的，这些纤维归因于蛋白质错误折叠。在这项研究中，我们使用生物物理方法研究了植物类黄酮多酚类黄酮中的槲皮素对鼠朊蛋白（moPrP）的抗淀粉样变性和抗氧化活性。结果表明，槲皮素结合到 moPrP 的 C 末端区域，并且槲皮素结合不影响 moPrP 的结构。然而，槲皮素结合加速 moPrP 纤维形成并改变 moPrP 纤维的结构。与典型的朊病毒纤维不同，槲皮素结合的纤维对蛋白酶 K敏感且结构松散。此外，由于类黄酮具有高抗氧化活性，因此槲皮素结合的纤维中不存在自由基失衡，因此对神经母细胞瘤细胞无毒。与典型的抗淀粉样变性药物不同，槲皮素显示出其独特性，这些药物要么抑制淀粉样蛋白的形成，要么消除已形成的淀粉样蛋白。槲皮素结合将 moPrP 转化为蛋白酶敏感且无毒的纤维。这项工作为抗淀粉样变性治疗的进展提供了有力的解决方案。
