Transactive response DNA-binding protein 43 kDa (TDP-43) is a highly conserved and widely expressed protein in human tissues that regulates nucleic acid processing. In frontotemporal dementia and amyotrophic lateral sclerosis, however, TDP-43 forms insoluble aggregates in central nervous tissues. These pathological deposits of TDP-43 have been primarily studied by ligand binding, namely western blot analysis, and, thus, methods with greater structural resolution are needed to aid in our understanding of the pathological processes associated with TDP-43 misfolding and aggregation. Toward this goal, we have developed a selective and multiplex method for the detection and characterization of TDP-43 using liquid chromatography tandem mass spectrometry. As proof-of-concept, the method was applied to the detection and characterization of TDP-43 in human cell lines and human brain tissue.

反式反应 DNA 结合蛋白 43 kDa (TDP-43) 是一种高度保守且在人体组织中广泛表达的蛋白质，可调节核酸加工。然而，在额颞叶痴呆和肌萎缩侧索硬化中，TDP-43 在中枢神经组织中形成不溶性聚集体。TDP-43 的这些病理沉积物主要通过配体结合进行研究，即蛋白质印迹分析，因此需要具有更高结构分辨率的方法来帮助我们了解与 TDP-43 错误折叠和聚集相关的病理过程。为了实现这一目标，我们开发了一种使用液相色谱串联质谱法检测和表征 TDP-43 的选择性和多重方法。作为概念验证，