Sharing of polyglutamine localization by the neuronal nucleus and cytoplasm in CAG‐repeat diseases
Sharing of polyglutamine localization by the neuronal nucleus and cytoplasm in CAG‐repeat diseases
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CAG 重复疾病中神经元核和细胞质共享多聚谷氨酰胺定位
DOI：
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发表时间：
2004
影响因子：
5
通讯作者：
H. Takahashi
中科院分区：
文献类型：
--
作者：
M. Yamada;C;C. Inenaga;S. Tsuji;H. Takahashi
三核苷酸胞嘧啶、腺嘌呤和鸟嘌呤(CAG)的扩增表明，多谷氨酰胺的密码是遗传性神经退行性疾病家族中常见的基因突变，包括马查多-约瑟夫病(MJD)和齿状核-苍白质萎缩(DRPLA)。泛素化神经元核内包涵体(NIIS)的存在被认为是这些疾病的神经病理特征，尽管NIIS在发病机制中的重要性仍然存在争议。在先前对DRLA的研究中，我们提出突变蛋白在核内的弥漫性堆积是神经元的另一个病理特征，这种特征的不同发生率可能与不同重复长度患者的临床症状的变化有关。最近，我们还披露了聚谷氨酰胺束定位于受影响神经元中的溶酶体的一个子集。目前对MJD和DRLA脑的免疫组织化学研究表明，病变神经元的核和胞浆共享扩张的聚谷氨酰胺束的亚细胞分布，这种分布模式是每个病变脑特有的。结果提示，在CAG-Repeat病中，突变蛋白同时参与泛素/蛋白酶体和内体/溶酶体的蛋白降解途径，在不同的神经细胞内，它们的积聚可能对神经元的生理产生不同的影响。
The expansion of a trinucleotide cytosine adenine and guanine (CAG) repeat that codes for polyglutamine is a common gene mutation in the family of hereditary neurodegenerative diseases that includes Machado‐Joseph disease (MJD) and dentatorubral‐pallidoluysian atrophy (DRPLA). The presence of ubiquitinated neuronal intranuclear inclusions (NIIs) has been recognized as a neuropathological hallmark of these diseases, although the significance of NIIs in the pathogenesis remains a matter of controversy. In a previous study of DRPLA, we proposed that intranuclear diffuse accumulation of mutant proteins is another pathological characteristic of neurones, and that the variable prevalence of this characteristic may be relevant to the variation of clinical symptoms in patients with different repeat sizes. Recently, we also disclosed that polyglutamine tracts are localized in a subset of lysosomes in affected neurones. The present immunohistochemical study of autopsied MJD and DRPLA brains shows that the nucleus and cytoplasm of affected neurones share the subcellular distribution of expanded polyglutamine tracts, the pattern of distribution being specific to each diseased brain. The results suggest that in CAG‐repeat diseases, mutant proteins are involved in both the ubiquitin/proteasome and endosomal/lysosomal pathways for protein degradation in different intraneuronal compartments, where their accumulation may exert distinct influences on neuronal physiology.
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DOI：
10.1098/rstb.1999.0449
发表时间：
1999-06-29
影响因子：
6.3
作者：
Cha, JHJ;Frey, AS;Young, AB
通讯作者：
Young, AB
DOI：
10.1073/pnas.96.20.11404
发表时间：
1999-09-28
影响因子：
11.1
作者：
Kazantsev, A;Preisinger, E;Housman, D
通讯作者：
Housman, D
影响因子：
56.9
作者：
DiFiglia, M;Sapp, E;Aronin, N
通讯作者：
Aronin, N
影响因子：
3.5
作者：
Luthi-Carter, R;Hanson, SA;Olson, JM
通讯作者：
Olson, JM