Mohammadi Soheila, Nikkhah Maryam, Hosseinkhani Saman
Department of Nanobiotechnology.
Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Int J Nanomedicine. 2017 Dec 14;12:8831-8840. doi: 10.2147/IJN.S144764. eCollection 2017.
The aggregation of alpha-synuclein (αS), natively unstructured presynaptic protein, is a crucial factor leading to the pathogenesis of Parkinson's disease (PD) and other related disorders. Recent studies have shown prefibrillar and oligomeric intermediates of αS as toxic to the cells. Herein, split-luciferase complementation assay is used to design a "signal-on" biosensor to monitor oligomerization of A53T αS inside the cells. Then, the effect of carbon-based nanomaterials, such as graphene quantum dots (GQDs) and graphene oxide quantum dots (GOQDs), on A53T αS oligomerization in vitro and in living cells is investigated. In this work, for the first time, it was found that GQDs at a concentration of 0.5 μg/mL can promote A53T αS aggregation by shortening the nucleation process, which is the key rate-determining step of fibrillation, thereby making a signal-on biosensor. While these nanomaterials may cross the blood-brain barrier because of their small sizes, the interaction between αS and GQDs may contribute to PD etiology.
α-突触核蛋白（αS）是一种天然无结构的突触前蛋白，其聚集是导致帕金森病（PD）及其他相关疾病发病机制的关键因素。最近的研究表明，αS的前纤维和寡聚中间体对细胞有毒性。在此，利用分裂荧光素酶互补分析设计了一种“信号开启”生物传感器，用于监测细胞内A53T αS的寡聚化。然后，研究了碳基纳米材料，如石墨烯量子点（GQDs）和氧化石墨烯量子点（GOQDs），对体外和活细胞中A53T αS寡聚化的影响。在这项工作中，首次发现浓度为0.5μg/mL的GQDs可以通过缩短成核过程来促进A53T αS聚集，而成核过程是纤维化的关键速率决定步骤，从而制成了一种“信号开启”生物传感器。虽然这些纳米材料可能因其尺寸小而穿过血脑屏障，但αS与GQDs之间的相互作用可能与PD病因有关。
