Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: Correlation between the density of inclusions and IT15 CAG triplet repeat length
Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: Correlation between the density of inclusions and IT15 CAG triplet repeat length
复制标题
DOI：
10.1006/nbdi.1998.0168
复制
发表时间：
1998-04-01
影响因子：
6.1
通讯作者：
Ross, CA
中科院分区：
文献类型：
--
作者：
Becher, MW;Kotzuk, JA;Ross, CA
亨廷顿氏病（HD）是由IT15中CAG三联体重复扩增引起的，这导致亨廷顿氏病蛋白产物亨廷顿蛋白中的聚谷氨酰胺延伸。HD的病理特征是神经元亚群的变性，主要是纹状体和新皮层的神经元亚群。虽然最近有报道称在转基因动物的神经元中有一种独特的核内包涵体表达编码亨廷顿蛋白n端部分（包括谷氨酰胺重复序列）的结构，但尚未在HD患者中发现受影响细胞的特异性形态学标记（Davies等，1997）。为了理解这一发现的重要性，我们在HD患者的尸检材料中寻找类似的核异常。在所有检查的20例HD病例中，抗泛素和n端亨廷顿蛋白抗体在神经元中鉴定出核内包涵体，这些病变的频率与IT15中CAG重复序列的长度相关。此外，检查相关的hd样三联体重复障碍，齿状体和苍白球萎缩的材料也显示核内神经元包涵体。这些发现提示含有蛋白聚集体的核内包涵体可能是谷氨酰胺重复神经退行性疾病发病机制的共同特征。(C) 1998学术出版社。
Huntington's disease (HD) is caused by CAG triplet repeat expansion in IT15 which leads to polyglutamine stretches in the HD protein product, huntingtin. The pathological hallmark of HD is the degeneration of subsets of neurons, primarily those in the striatum and neocortex. Specific morphological markers of affected cells have not been identified in patients with HD, although a unique intranuclear inclusion was recently reported in neurons of transgenic animals expressing a construct encoding the N-terminal part (including the glutamine repeat) of huntingtin (Davies ef at, 1997). In order to understand the importance of this finding, we sought for comparable nuclear abnormalities in autopsy material from patients with HD. In all 20 HD cases examined, anti-ubiquitin and N-terminal huntingtin antibodies identified intranuclear inclusions in neurons and the frequency of these lesions correlated with the length of the CAG repeat in IT15. In addition, examination of material from the related HD-like triplet repeat disorder, dentatorubral and pallidoluysian atrophy, also revealed intranuclear neuronal inclusions. These findings suggest that intranuclear inclusions containing protein aggregates may be a common feature of the pathogenesis of glutamine repeat neurodegenerative disorders. (C) 1998 Academic Press.