Translational Neuropathology Research Laboratory, Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 605B Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Nat Rev Neurosci. 2011 Nov 30;13(1):38-50. doi: 10.1038/nrn3121.
RNA-binding proteins, and in particular TAR DNA-binding protein 43 (TDP43), are central to the pathogenesis of motor neuron diseases and related neurodegenerative disorders. Studies on human tissue have implicated several possible mechanisms of disease and experimental studies are now attempting to determine whether TDP43-mediated neurodegeneration results from a gain or a loss of function of the protein. In addition, the distinct possibility of pleotropic or combined effects - in which gains of toxic properties and losses of normal TDP43 functions act together - needs to be considered.
RNA 结合蛋白，特别是 TAR DNA 结合蛋白 43（TDP43），是运动神经元疾病和相关神经退行性疾病发病机制的核心。对人体组织的研究提示了几种可能的疾病机制，而实验研究目前正试图确定 TDP43 介导的神经退行性变是源自蛋白功能获得还是丧失。此外，还需要考虑到可能存在的多效性或联合效应，即毒性特性的获得和正常 TDP43 功能的丧失共同作用。
