The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia.
The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia.
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DOI：
10.1097/wco.0b013e3283168d1d
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发表时间：
2008-12
影响因子：
4.8
通讯作者：
Rademakers R
中科院分区：
文献类型：
--
作者：
Mackenzie IR;Rademakers R
我们研究了目前的证据表明，TAR DNA结合蛋白，TDP-43，在肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）的致病作用。TDP-43最近被鉴定为散发性ALS和FTD最常见病理亚型（伴泛素化包涵体的额颞叶变性（FLTD-U））中的主要病理蛋白。在这些条件下，TDP-43的异常C-末端片段被泛素化、过度磷酸化，并在神经元和神经胶质中积累为细胞内含物。具有内含物的细胞显示正常核TDP-43定位的缺失。最近，在散发性和家族性ALS患者中发现了编码TDP-43的基因的错义突变。最近在ALS和FTLD-U中发现的病理性TDP-43证实了这些是神经退行性疾病的新生化类别TDP-43蛋白质病中密切相关的病症。
We examine current evidence that the TAR DNA binding protein, TDP-43, plays a pathogenic role in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 was recently identified as the major pathological protein in sporadic ALS and in the most common pathological subtype of FTD, frontotemporal lobar degeneration with ubiquitinated inclusions (FLTD-U). In these conditions, abnormal C-terminal fragments of TDP-43 are ubiquitinated, hyperphosphorylated and accumulate as cellular inclusions in neurons and glia. Cells with inclusions show absence of the normal nuclear TDP-43 localization. Recently, missense mutations in the gene encoding TDP-43 have been identified in patients with sporadic and familial ALS. The recent discovery of pathological TDP-43 in both ALS and FTLD-U confirms that these are closely related conditions within a new biochemical class of neurodegenerative disease, the TDP-43 proteinopathies.