Autophagy-related proteins (p62, NBR1 and LC3) in intranuclear inclusions in neurodegenerative diseases
Autophagy-related proteins (p62, NBR1 and LC3) in intranuclear inclusions in neurodegenerative diseases
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DOI：
10.1016/j.neulet.2012.06.026
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发表时间：
2012-08-01
影响因子：
2.5
通讯作者：
Wakabayashi, Koichi
中科院分区：
文献类型：
--
作者：
Mori, Fumiaki;Tanji, Kunikazu;Wakabayashi, Koichi
据报道，在多种神经退行性疾病中，泛素和泛素相关蛋白（包括 p62）掺入神经元核内包涵体 (NII)。然而，NIIs 中自噬特异性蛋白（NBR1 和 LC3）的参与尚未被提及。我们使用针对泛素、p62、NBR1 和 LC3 的抗体，对马查多-约瑟夫病 (MJD；n = 5)、齿状红核苍白球路易体萎缩症 (DRPLA；n = 5) 和核内包涵体病 (INIBD；n = 5) 患者的大脑进行了免疫组织化学检查。在每种情况下计算 p62-、NBR1- 和 LC3- 阳性内含物相对于泛素阳性内含物数量的比例。 MJD (19.3%)、DRPLA (49.7%) 和 INIBD (99.8%) 的 NII 中 p62 呈阳性。至于自噬特异性蛋白，MID（4.2％）、DRPLA（5.5％）和INIBD（13.2％）中NIIs呈NBR1阳性，MJD中LC3呈阴性。 DRPLA 和 INIBD，1 例 INIBD 除外。这些发现表明自噬-溶酶体途径不参与 NII 的形成/降解。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。
Incorporation of ubiquitin and ubiquitin-related proteins including p62 into neuronal intranuclear inclusions (NIIs) has been reported in a variety of neurodegenerative diseases. However, involvement of autophagy-specific proteins (NBR1 and LC3) in NIIs has not been mentioned. We immunohistochemically examined the brain of patients with Machado-Joseph disease (MJD; n = 5), dentatorubral-pallidoluysian atrophy (DRPLA; n = 5) and intranuclear inclusion body disease (INIBD; n = 5), using antibodies against ubiquitin, p62, NBR1 and LC3. The proportion of p62-, NBR1- and LC3-positive inclusions relative to the number of ubiquitin-positive inclusions was calculated in each case. NIIs were positive for p62 in MJD (19.3%), DRPLA (49.7%) and INIBD (99.8%). As for autophagy-specific proteins, NIIs were positive for NBR1 in MID (4.2%), DRPLA (5.5%) and INIBD (13.2%) and negative for LC3 in MJD. DRPLA and INIBD, except for one case of INIBD. These findings suggest that autophagy-lysosome pathway is not involved in the formation/degradation of NIIs. (C) 2012 Elsevier Ireland Ltd. All rights reserved.