Needham Lisa-Maria, Weber Judith, Fyfe James W B, Kabia Omaru M, Do Dung T, Klimont Ewa, Zhang Yu, Rodrigues Margarida, Dobson Christopher M, Ghandi Sonia, Bohndiek Sarah E, Snaddon Thomas N, Lee Steven F
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge, CB3 0HE, UK.
R Soc Open Sci. 2018 Feb 7;5(2):171399. doi: 10.1098/rsos.171399. eCollection 2018 Feb.
Protein aggregation into amyloid deposits and oxidative stress are key features of many neurodegenerative disorders including Parkinson's and Alzheimer's disease. We report here the creation of four highly sensitive bifunctional fluorescent probes, capable of HO and/or amyloid aggregate detection. These bifunctional sensors use a benzothiazole core for amyloid localization and boronic ester oxidation to specifically detect HO. We characterized the optical properties of these probes using both bulk fluorescence measurements and single-aggregate fluorescence imaging, and quantify changes in their fluorescence properties upon addition of amyloid aggregates of α-synuclein and pathophysiological HO concentrations. Our results indicate these new probes will be useful to detect and monitor neurodegenerative disease.
蛋白质聚集成淀粉样沉积物和氧化应激是包括帕金森病和阿尔茨海默病在内的许多神经退行性疾病的关键特征。我们在此报告了四种高灵敏度双功能荧光探针的创制,它们能够检测羟基自由基(HO)和/或淀粉样聚集体。这些双功能传感器利用苯并噻唑核心进行淀粉样物质定位,并通过硼酸酯氧化来特异性检测羟基自由基。我们使用体相荧光测量和单聚集体荧光成像对这些探针的光学性质进行了表征,并对添加α-突触核蛋白的淀粉样聚集体和病理生理浓度的羟基自由基后其荧光性质的变化进行了量化。我们的结果表明,这些新型探针将有助于检测和监测神经退行性疾病。