Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Neurol India. 2013 Mar-Apr;61(2):107-10. doi: 10.4103/0028-3886.111109.
Amyotrophic lateral sclerosis (ALS) typically commences in a discrete location in a limb or bulbar territory muscles and then spreads to the adjacent anatomical regions. This pattern is consistent with a contiguous spread of the disease process in motor neuron network resulting in progressive motor weakness. The etiology of ALS onset and the mechanism of the regional ALS spread remain elusive. Over the past 5 years, identification of mutations in two RNA binding proteins, trans active response (TAR) DNA-binding protein (TDP-43) and fused in sarcoma (FUS), in patients with familial ALS has led to a major shift in our understanding of the ALS disease mechanism. In addition to their role in RNA metabolism, TDP-43 and FUS form protein aggregates in the affected neurons. More recent findings demonstrating that both TDP-43 and FUS contain glutamine/asparagine (Q/N) residue-rich prion-like domains have spurred intense research interest. This brief review discusses the prion-related domains in TDP-43 and FUS and their implication in protein aggregate formation and disease spread in ALS.
肌萎缩侧索硬化症（ALS）通常起始于肢体或延髓区域肌肉的一个特定位置，然后扩散到相邻的解剖区域。这种模式与运动神经元网络中疾病过程的连续扩散一致，导致进行性运动无力。ALS 发病的病因和区域 ALS 扩散的机制仍不清楚。在过去的 5 年中，在家族性 ALS 患者中鉴定出两种 RNA 结合蛋白，反式激活反应（TAR）DNA 结合蛋白（TDP-43）和肉瘤融合（FUS）中的突变，使我们对 ALS 疾病机制的理解发生了重大转变。除了在 RNA 代谢中的作用外，TDP-43 和 FUS 在受影响的神经元中形成蛋白质聚集体。最近的发现表明，TDP-43 和 FUS 都含有富含谷氨酰胺/天冬酰胺（Q/N）残基的朊病毒样结构域，这激发了强烈的研究兴趣。本文简要综述了 TDP-43 和 FUS 中的朊病毒相关结构域及其在 ALS 中蛋白质聚集体形成和疾病扩散中的作用。
