Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, NSW, Australia.
Int J Biochem Cell Biol. 2010 Oct;42(10):1606-9. doi: 10.1016/j.biocel.2010.06.016. Epub 2010 Jun 25.
Transactive response DNA binding protein 43 kDa (TDP-43) is a DNA and RNA binding protein involved in RNA processing and with structural resemblance to heterogeneous ribonucleoproteins (hnRNPs). TDP-43 serves multiple functions with roles in transcriptional regulation, pre-mRNA splicing and translational regulation. TDP-43 is also crucial for embryonic development with increasing evidence indirectly implicating its involvement in other cellular processes including microRNA biogenesis, apoptosis and cell division. The role of TDP-43 in neurodegeneration has been actively studied since identification as a major component of the ubiquitinated inclusions seen in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TDP-43 pathology has also been identified in several other neurodegenerative diseases. These disorders are collectively referred to as TDP-43 proteinopathies. The identification of rare TDP-43 mutations in sporadic and familial forms of ALS and FTLD suggests TDP-43 plays an important pathogenic role, rather than merely being a marker of the disease.
转激活反应 DNA 结合蛋白 43kDa（TDP-43）是一种参与 RNA 加工的 DNA 和 RNA 结合蛋白，其结构与异质核核糖核蛋白（hnRNPs）相似。TDP-43 具有多种功能，在转录调控、前体 mRNA 剪接和翻译调控中发挥作用。TDP-43 对胚胎发育也至关重要，越来越多的证据间接表明其参与了其他细胞过程，包括 microRNA 生物发生、细胞凋亡和细胞分裂。TDP-43 作为肌萎缩侧索硬化症（ALS）和额颞叶变性（FTLD）中所见的泛素化包含物的主要成分，自被鉴定以来，其在神经退行性变中的作用一直受到积极研究。TDP-43 病理学也在几种其他神经退行性疾病中得到了鉴定。这些疾病统称为 TDP-43 蛋白病。在散发性和家族性 ALS 和 FTLD 中罕见 TDP-43 突变的鉴定表明，TDP-43 发挥了重要的致病作用，而不仅仅是疾病的标志物。
