A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114
A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114
复制标题
DOI：
10.1046/j.1471-4159.2003.01949.x
复制
发表时间：
2003-09-01
影响因子：
4.7
通讯作者：
Lee, VMY
中科院分区：
文献类型：
--
作者：
Crystal, AS;Giasson, BI;Lee, VMY
具有淀粉样蛋白生成特性的蛋白质内含物是许多神经退行性疾病（包括阿尔茨海默病和帕金森病）之间的常见联系。淀粉样纤维的组织学和体外研究已经推进了对蛋白质聚集的理解，并为这些神经退行性脑淀粉样变性的致病机制提供了重要的见解。经典的淀粉样蛋白染料刚果红（CR）和硫磺素T和S已被广泛用于原位检测淀粉样蛋白包涵体。这些染料也已被用来监测成熟的淀粉样蛋白原纤维组装从单体亚基在体外。最近，由CR结构衍生的化合物（trans-trans，trans-l-bromo-2，5-bis-（3-hydroxycarbonyl-4-hydroxy）styrylbenzene，BSB）被证明与广泛的淀粉样蛋白包涵体原位结合。更重要的是，它也被用于标记活体动物的脑淀粉样蛋白。在本文中，我们表明，BSB的类似物，（反式，反式）-1-溴-2，5-双-（4-羟基）苯乙烯基苯（K114），识别淀粉样病变，并具有独特的性能，允许定量监测的淀粉样纤维的形成组装的淀粉样β肽，α-突触核蛋白，和tau蛋白。
Proteinaceous inclusions with amyloidogenic properties are a common link between many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Histological and in vitro studies of amyloid fibrils have advanced the understanding of protein aggregation, and provided important insights into pathogenic mechanisms of these neurodegenerative brain amyloidoses. The classical amyloid dyes Congo Red (CR) and thioflavin T and S, have been used extensively to detect amyloid inclusions in situ. These dyes have also been utilized to monitor the maturation of amyloid fibrils assembled from monomer subunits in vitro. Recently, the compound (trans, trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB), derived from the structure of CR, was shown to bind to a wide range of amyloid inclusions in situ. More importantly it was also used to label brain amyloids in live animals. Herein, we show that an analogue of BSB, (trans, trans)-1-bromo-2,5-bis-(4-hydroxy)styrylbenzene (K114), recognizes amyloid lesions, and has distinctive properties which allowed the quantitative monitoring of the formation of amyloid fibrils assembled from the amyloid-beta peptide, alpha-synuclein, and tau.