Neuronal intranuclear hyaline inclusion disease with polyglutamine-immunoreactive inclusions
Neuronal intranuclear hyaline inclusion disease with polyglutamine-immunoreactive inclusions
复制标题
伴有多聚谷氨酰胺免疫反应性包涵体的神经元核内透明包涵体病
作者：
J. Takahashi;T. Fukuda;J. Tanaka;M. Minamitani;H. Fujigasaki;T. Uchihara
神经元核内透明蛋白包涵体病（NIHID）是一组以神经元核内包涵体存在为特征的神经退行性疾病。我们在此报告一位25岁女性患者的临床病理结果，她在13年的临床病程后死亡，其特征是进行性步态障碍和运动障碍。组织学检查显示广泛的NIs伴局限性区域神经元丢失；丘脑下核、内白质、黑质、Edinger-Westphal核和浦肯野细胞层神经元丢失严重。NIs的量化与神经元损失的分级评估相结合，揭示了一个总体趋势，即更严重的神经元损失伴随着更低的NIs频率。与最近在几种CAG重复疾病中发现的核包涵体形态相似，促使我们检查泛素的免疫定位和扩大的聚谷氨酰胺延伸，这表明泛素存在于大多数NIs的外围。在少数NIs中心可见扩大的聚谷氨酰胺拉伸。这些发现表明异常片段，如扩大的聚谷氨酰胺区域被纳入包膜，聚集在其中心，从而通过泛素依赖的蛋白水解途径代谢。尽管NIs的形成与神经元退化的关系尚不清楚，但我们的研究结果表明，NIs是在隔离或降解异常蛋白片段的过程中形成的，NIs的形成可能不会立即对神经元产生毒性。
Abstract Neuronal intranuclear hyaline inclusion disease (NIHID) is a group of neurodegenerative disorders characterized by the presence of intranuclear inclusions in neurons (NIs). We report here clinicopathological findings of a 25-year-old female patient who died after 13 years of a clinical course characterized by progressive gait disturbance and movement disorders. Histological examination revealed widespread NIs with neuronal loss in restricted regions; neuronal loss was severe in the subthalamic nucleus, internal pallidum, substantia nigra, Edinger-Westphal nucleus and Purkinje cell layer. Quantification of the NIs combined with a graded evaluation of neuronal loss revealed an overall tendency for more severe neuronal loss to be accompanied by a lower frequency of NIs. A morphological similarity to the nuclear inclusions recently identified in several CAG repeat diseases prompted us to examine the immunolocalization of ubiquitin and expanded polyglutamine stretches, which demonstrated the presence of ubiquitin at the periphery of most NIs. An expanded polyglutamine stretch was seen in the center of limited number of NIs. These findings indicate that abnormal fragments such as expanded polyglutamine regions are incorporated into the inclusion, aggregated in its center, and thereby metabolized by a ubiquitin-dependent proteolytic pathway. Although it remains to be elucidated how the formation of NIs is related to neuronal degeneration, our findings suggest that NIs are formed in the process of sequestering or degrading abnormal protein fragments and formation of NIs may not be immediately toxic to neurons.
影响因子：
56.9
作者：
DiFiglia, M;Sapp, E;Aronin, N
通讯作者：
Aronin, N