Crystal Adam S, Giasson Benoit I, Crowe Alexander, Kung Mei-Ping, Zhuang Zhi-Ping, Trojanowski John Q, Lee Virginia M-Y
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Neurochem. 2003 Sep;86(6):1359-68. doi: 10.1046/j.1471-4159.2003.01949.x.
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.
具有淀粉样蛋白生成特性的蛋白质内含物是包括阿尔茨海默病和帕金森病在内的许多神经退行性疾病之间的共同联系。淀粉样纤维的组织学和体外研究推动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见解。经典的淀粉样蛋白染料刚果红（CR）、硫黄素T和S已被广泛用于原位检测淀粉样蛋白内含物。这些染料也被用于监测体外由单体亚基组装而成的淀粉样纤维的成熟过程。最近，一种源自CR结构的化合物（反式，反式）-1-溴-2,5-双-（3-羟基羰基-4-羟基）苯乙烯基苯（BSB）被证明能原位结合多种淀粉样蛋白内含物。更重要的是，它还被用于标记活体动物脑中的淀粉样蛋白。在此，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）能够识别淀粉样病变，并且具有独特的特性，可对由淀粉样β肽、α-突触核蛋白和tau组装而成的淀粉样纤维的形成进行定量监测。
