Department of Chemistry, Oakland University, Rochester, MI, 48309, USA.
Department of Forensic Science, Environmental and Life Sciences, Trent University, Peterborough, ON, K9L 0G2, Canada.
Anal Bioanal Chem. 2020 Feb;412(5):1193-1201. doi: 10.1007/s00216-019-02350-8. Epub 2020 Jan 3.
Neurodegeneration currently remains without a differential diagnosis or cure. Tau protein is one of the biomarkers of neurodegenerative diseases commonly known as tauopathies. Tau protein plays an integral role in stabilizing microtubules and cell structure; however, due to post-translational modifications, tau protein undergoes self-assembly into cytotoxic structures and is co-localized intra- and extracellularly. Hence, tau protein is a viable biomarker associated with protein pathogenesis and neurodegeneration. The novel optical biosensor for tau441 protein is based on the aptamer recognition probe and the biolayer interferometry (BLI) method for detection. The current biotin-aptasensor in combination with the streptavidin surface provides real-time monitoring of tau441 protein in the nanomolar range, with the limit of detection at 6.7 nM in vitro. The tau441 detection is achieved with high selectivity over other neurodegeneration biomarkers which include amyloid-β and α-synuclein. The aptasensor also allows for tau441 protein detection in a complex matrix such as fetal bovine serum, indicating its utility in other biological fluids for diagnostic applications. The optical method is simple, rapid and highly selective for point-of-care application which is critical for achieving the early and differential diagnosis of neurodegenerative diseases and identifying their treatments. Graphical abstract.
神经退行性疾病目前仍然无法进行鉴别诊断或治愈。tau 蛋白是神经退行性疾病(通常称为 tau 病)的生物标志物之一。tau 蛋白在稳定微管和细胞结构方面发挥着重要作用;然而,由于翻译后修饰,tau 蛋白会自我组装成细胞毒性结构,并在细胞内和细胞外共定位。因此,tau 蛋白是一种与蛋白发病机制和神经退行性变相关的可行生物标志物。tau441 蛋白的新型光学生物传感器基于适体识别探针和生物层干涉 (BLI) 方法进行检测。目前的生物素适体传感器与链霉亲和素表面相结合,可实时监测纳摩尔范围内的 tau441 蛋白,体外检测限为 6.7 nM。tau441 的检测具有高度选择性,可区分其他神经退行性变生物标志物,包括淀粉样蛋白-β和α-突触核蛋白。该适体传感器还可用于检测胎牛血清等复杂基质中的 tau441 蛋白,表明其可用于其他生物体液中的诊断应用。该光学方法简单、快速且高度选择性,可用于即时诊断,对于实现神经退行性疾病的早期和鉴别诊断以及确定其治疗方法至关重要。图表摘要。