Detection of α-Synuclein Amyloidogenic Aggregates in Vitro and in Cells using Light-Switching Dipyridophenazine Ruthenium(II) Complexes
Detection of α-Synuclein Amyloidogenic Aggregates in Vitro and in Cells using Light-Switching Dipyridophenazine Ruthenium(II) Complexes
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DOI：
10.1021/ja3100287
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发表时间：
2012-12-26
影响因子：
15
通讯作者：
Marti, Angel A.
中科院分区：
文献类型：
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作者：
Cook, Nathan P.;Kilpatrick, Kiri;Marti, Angel A.
蛋白质聚集是许多神经退行性疾病的标志，包括帕金森病和亨廷顿病。有一个显着的兴趣，了解在体内和体外的单体可溶性蛋白质的自缔合和成不溶性沉积物的fietrization所涉及的分子机制。具有新特性的探针，如红移发射，大斯托克斯位移，和高光稳定性，是各种蛋白质聚集研究所需的。为了满足对适于细胞研究的聚集响应化合物的日益增长的需求，我们提出了钌（II）二吡啶并吩嗪衍生物，[Ru（phen）（2）dppz]（2+）（phen = 1，10-菲咯啉，dppz =二吡啶并[3，2-a：2 '.3 '-c]吩嗪），以研究与帕金森病的发展相关的α-突触核蛋白（α S）的聚集。我们证明了使用[Ru（phen）（2）dppz]（2+）来实时监测alpha S原纤维的形成，并检测和定量神经胶质瘤细胞中的alpha S聚集体，从而为体外和体内研究蛋白质沉积疾病提供了一种新的分子工具。
Protein aggregation is the hallmark of a number of neurodegenerative diseases including Parkinson's and Huntington's diseases. There is a significant interest in understanding the molecular mechanisms involved in the self-association and fibrillization of monomeric soluble proteins into insoluble deposits in vivo and in vitro. Probes with novel properties, such as red-shifted emission, large Stokes shifts, and high photostability, are desirable for a variety of protein aggregation studies. To respond to the increasing need for aggregation responsive compounds suitable to cellular studies, we present a ruthenium(II) dipyridophenazine derivative, [Ru(phen)(2)dppz](2+) (phen =1,10-phenanthroline, dppz = dipyrido[3,2-a:2 '.3 '-c]phenazine), to study aggregation of alpha-synuclein (alpha S), which is associated with the development of Parkinson's disease. We demonstrated the use of [Ru(phen)(2)dppz](2+) to monitor alpha S fibril formation in real-time and to detect and quantify alpha S aggregates in neuroglioma cells, thereby providing a novel molecular tool to study protein deposition diseases in vitro and in vivo.