International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
Curr Alzheimer Res. 2011 May;8(3):237-45. doi: 10.2174/156720511795563719.
Two proteins have recently received considerable attention in the neurodegenerative research field: TDP-43 and FUS/TLS. The reason is that both proteins have been found to represent major protein components of the intracellular inclusions occurring in the neuronal tissues of patients affected by Fronto Temporal Lobar Degeneration and Amyotrophic Lateral Sclerosis. One of the most interesting features of this discovery is that both proteins have in common several structural properties. In particular, they are multifunctional RNA-binding proteins (RBPs) already known to play a role in several cellular processes such as transcription, pre-mRNA splicing, and mRNA stability. The potential consequences of changes in their intracellular localization and protein modification status (phosphorylation, ubiquitination, and cleavage) on neuronal metabolism represent one of the major research challenges faced today by researchers. There is hope that a detailed knowledge of the gain- or loss-of-function mechanisms mediated by alterations in these proteins in the neuronal environment may provide novel therapeutic strategies for the treatment of these diseases. Here, we aim to provide an updated review of ways by which TDP-43 and FUS/TLS influence gene expression. In particular, we will focus on the characterized properties of both proteins that involve gene transcription and also RNA splicing, transport and stability processes.
TDP-43 和 FUS/TLS。原因是这两种蛋白质都被发现代表了额颞叶变性和肌萎缩侧索硬化症患者神经元组织中细胞内包涵体的主要蛋白质成分。这一发现最有趣的特征之一是，这两种蛋白质具有几个共同的结构特性。它们都是多功能 RNA 结合蛋白（RBPs），已知在转录、前体 mRNA 剪接和 mRNA 稳定性等多种细胞过程中发挥作用。它们在细胞内定位和蛋白质修饰状态（磷酸化、泛素化和切割）改变对神经元代谢的潜在影响是研究人员目前面临的主要研究挑战之一。人们希望，对这些蛋白质在神经元环境中改变介导的功能获得或丧失机制的详细了解，可能为这些疾病的治疗提供新的治疗策略。在这里，我们旨在提供 TDP-43 和 FUS/TLS 影响基因表达的方式的最新综述。特别是，我们将重点介绍这两种蛋白质的特性，包括涉及基因转录以及 RNA 剪接、运输和稳定性过程的特性。
