TAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process In neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various types of RNA, such as mRNA, microRNA, and circular RNA. These changes can result in the generation of an altered transcriptome and proteome within cells, ultimately changing the diversity and quantity of gene products. In this review, we summarise the findings of novel atypical RNAs resulting from TDP-43 dysfunction and their potential as biomarkers or targets for therapeutic development.

中文翻译：

---

了解 TDP-43 功能与年龄相关的病理变化以及对健康和疾病中 RNA 剪接和信号传导的影响

TAR DNA 结合蛋白-43 (TDP-43) 是 RNA 剪接的关键成分，在衰老过程中发挥着至关重要的作用。在神经退行性疾病中，如肌萎缩侧索硬化症、额颞叶痴呆和边缘主导型年龄相关性 TDP-43 脑病， TDP-43 可能发生突变、错位到神经元和神经胶质细胞的细胞核外，并形成细胞质内含物。这些 TDP-43 改变可导致其 RNA 剪接失调，并导致各种类型 RNA（例如 mRNA、microRNA 和环状 RNA）的错误剪接。这些变化可能导致细胞内转录组和蛋白质组发生改变，最终改变基因产物的多样性和数量。在这篇综述中，我们总结了 TDP-43 功能障碍引起的新型非典型 RNA 的发现及其作为治疗开发的生物标志物或靶点的潜力。