Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain
Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain
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DOI：
10.1126/science.277.5334.1990
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发表时间：
1997-09-26
期刊：
影响因子：
56.9
通讯作者：
Aronin, N
中科院分区：
文献类型：
--
作者：
DiFiglia, M;Sapp, E;Aronin, N
亨廷顿病（HD）神经变性的原因尚不清楚。HD患者亨廷顿蛋白的NH 2-末端多聚谷氨酰胺区域扩大。突变亨廷顿蛋白的NH 2-末端片段被定位于神经元核内包涵体（NIIs）和营养不良的神经突（DNs）在HD皮质和纹状体，这是在HD的影响，和多聚谷氨酰胺的长度影响亨廷顿蛋白在这些结构中积累的程度。在NII和DN中也发现了泛素，这表明异常亨廷顿蛋白是蛋白水解的目标，但对去除具有抗性。突变亨廷顿蛋白的聚集可能是HD发病机制的一部分。
The cause of neurodegeneration in Huntington's disease (HD) is unknown. Patients with HD have an expanded NH2-terminal polyglutamine region in huntingtin. An NH2-terminal fragment of mutant huntingtin was localized to neuronal intranuclear inclusions (NIIs) and dystrophic neurites (DNs) in the HD cortex and striatum, which are affected in HD, and polyglutamine length influenced the extent of huntingtin accumulation in these structures. Ubiquitin was also found in NIIs and DNs, which suggests that abnormal huntingtin is targeted for proteolysis but is resistant to removal. The aggregation of mutant huntingtin may be part of the pathogenic mechanism in HD.