Yu Kun-Hua, Lee Cheng-I
Department of Biomedical Sciences, Center for Nano Bio-Detections and Center for Innovative Research on Aging Society (CIRAS), National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan.
Pharmaceutics. 2020 Nov 11;12(11):1081. doi: 10.3390/pharmaceutics12111081.
Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by misfolding and aggregation of prion protein (PrP). Previous studies have demonstrated that quercetin can disaggregate some amyloid fibrils, such as amyloid β peptide (Aβ) and α-synuclein. However, the disaggregating ability is unclear in PrP fibrils. In this study, we examined the amyloid fibril-disaggregating activity of quercetin on mouse prion protein (moPrP) and characterized quercetin-bound moPrP fibrils by imaging, proteinase resistance, hemolysis assay, cell viability, and cellular oxidative stress measurements. The results showed that quercetin treatment can disaggregate moPrP fibrils and lead to the formation of the proteinase-sensitive amorphous aggregates. Furthermore, quercetin-bound fibrils can reduce the membrane disruption of erythrocytes. Consequently, quercetin-bound fibrils cause less oxidative stress, and are less cytotoxic to neuroblastoma cells. The role of quercetin is distinct from the typical function of antiamyloidogenic drugs that inhibit the formation of amyloid fibrils. This study provides a solution for the development of antiamyloidogenic therapy.
传染性海绵状脑病（TSEs）是由朊病毒蛋白（PrP）错误折叠和聚集引起的致命性神经退行性疾病。先前的研究表明，槲皮素可以使一些淀粉样纤维解聚，如淀粉样β肽（Aβ）和α-突触核蛋白。然而，槲皮素对PrP纤维的解聚能力尚不清楚。在本研究中，我们检测了槲皮素对小鼠朊病毒蛋白（moPrP）的淀粉样纤维解聚活性，并通过成像、蛋白酶抗性、溶血试验、细胞活力和细胞氧化应激测量对与槲皮素结合的moPrP纤维进行了表征。结果表明，槲皮素处理可以使moPrP纤维解聚，并导致形成蛋白酶敏感的无定形聚集体。此外，与槲皮素结合的纤维可以减少红细胞的膜破坏。因此，与槲皮素结合的纤维引起的氧化应激较小，对神经母细胞瘤细胞的细胞毒性也较小。槲皮素的作用不同于抑制淀粉样纤维形成的抗淀粉样生成药物的典型功能。本研究为抗淀粉样生成疗法的开发提供了一种解决方案。
