TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
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DOI：
10.1016/j.bbrc.2006.10.093
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发表时间：
2006-12-22
影响因子：
3.1
通讯作者：
Oda, Tatsuro
中科院分区：
文献类型：
--
作者：
Arai, Tetsuaki;Hasegawa, Masato;Oda, Tatsuro
泛素阳性tau阴性神经元细胞质包涵体和营养不良的神经突是伴有或不伴有运动神经元疾病症状的额颞叶变性（FTLD）和肌萎缩性侧索硬化症（ALS）的常见病理特征。通过生化和免疫组织化学分析，我们发现了一个43 kDa的TAR dna结合蛋白（TDP-43），这是一种调节转录和选择性剪接的核因子，是FTLD中这些结构的一个组成部分。此外，ALS患者脊髓的束状包涵体、神经元核内包涵体和胶质包涵体也呈TDP-43阳性。对萨科基不溶性部分的去磷酸化处理表明，积累的TDP-43发生异常磷酸化。TDP-43在细胞内积聚的常见现象支持了这些疾病代表单一疾病的临床病理实体的假设，并提示它们可以被新分类为TDP-43的蛋白质病。(c) 2006爱思唯尔公司版权所有。
Ubiquitin-positive tau-negative neuronal cytoplasmic inclusions and dystrophic neurites are common pathological features in frontotemporal lobar degeneration (FTLD) with or without symptoms of motor neuron disease and in amyotrophic lateral sclerosis (ALS). Using biochemical and immunohistochemical analyses, we have identified a TAR DNA-binding protein of 43 kDa (TDP-43), a nuclear factor that functions in regulating transcription and alternative splicing, as a component of these structures in FTLD. Furthermore, skein-like inclusions, neuronal intranuclear inclusions, and glial inclusions in the spinal cord of ALS patients are also positive for TDP-43. Dephosphorylation treatment of the sarkosyl insoluble fraction has shown that abnormal phosphorylation takes place in accumulated TDP-43. The common occurrence of intracellular accumulations of TDP-43 supports the hypothesis that these disorders represent a clinicopathological entity of a single disease, and suggests that they can be newly classified as a proteinopathy of TDP-43. (c) 2006 Elsevier Inc. All rights reserved.