Neuronal intranuclear hyaline inclusion disease
Neuronal intranuclear hyaline inclusion disease
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DOI：
10.1046/j.1440-1789.2003.00524.x
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发表时间：
2003-12-01
期刊：
影响因子：
2.3
通讯作者：
Takahashi-Fujigasaki, J
中科院分区：
文献类型：
--
作者：
Takahashi-Fujigasaki, J
神经元核内透明蛋白包涵体病（NIHID）是一种罕见的神经退行性疾病，其病理特征是神经元和胶质细胞中存在嗜酸性核内包涵体。它被认为是一种异质性疾病实体，因为以前描述的病例的临床图片是高度可变的。在本综述中，已报道的NIHID病例根据发病和病程分为三个临床亚组，并讨论了每个亚组的临床表型。NIHID中的神经元核内包涵体（NII）泛素化，其发生率与神经元丢失呈负相关，表明NII的形成是一种涉及泛素-蛋白酶体依赖的蛋白水解途径的保护机制。在一些多聚谷氨酰胺疾病中，含有异常扩张的多聚谷氨酰胺束的疾病相关蛋白聚集在神经元核中，导致NII的形成。NIHID中的NII与多谷氨酰胺疾病之间的相似性表明它们是在细胞核中发生的共同蛋白水解相关过程中形成的。尽管NIHID的发病机制尚不清楚，但本文回顾的数据表明，它可能与尚未识别的异常蛋白的积累或核内泛素-蛋白酶体途径的功能障碍有关。
Neuronal intranuclear hyaline inclusion disease (NIHID) is a rare neurodegenerative disorder characterized pathologically by the presence of eosinophilic intranuclear inclusions in neuronal and glial cells. It has been considered to be a heterogeneous disease entity because the clinical pictures of previously described cases were highly variable. In the present review, reported NIHID cases have been categorized into three clinical subgroups according to onset and disease duration, and the clinical phenotype of each subgroup is discussed. Neuronal intranuclear inclusions (NII) in NIHID are ubiquitinated and their prevalence is inversely correlated with neuronal loss, suggesting that NII formation is a protective mechanism involving the ubiquitin-proteasome-dependent proteolytic pathway. In several polyglutamine diseases, disease-related proteins containing abnormally expanded polyglutamine tracts aggregate in neuronal nuclei, resulting in NII formation. The similarity between NII in NIHID and polyglutamine diseases suggests that they are formed during a common proteolysis-related process that takes place in the nucleus. Although the pathogenetic mechanism underlying NIHID remains unknown, the data reviewed here suggest that it might be related to accumulation of as yet unidentified abnormal proteins or dysfunction of the intranuclear ubiquitin-proteasome pathway.