LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains.
LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains.
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DOI：
10.1186/1750-1172-9-68
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发表时间：
2014-05-01
影响因子：
3.7
通讯作者：
Arima K
中科院分区：
文献类型：
--
作者：
Satoh J;Motohashi N;Kino Y;Ishida T;Yagishita S;Jinnai K;Arai N;Nakamagoe K;Tamaoka A;Saito Y;Arima K
Nasu-Hakola病（NHD）是一种罕见的常染色体隐性遗传疾病，其特征是由DAP 12或TREM 2的功能丧失突变引起的硬化性白质脑病和多灶性骨囊肿。TREM 2和DAP 12构成受体/接头信号传导复合物，其仅在破骨细胞、树突细胞、巨噬细胞和小胶质细胞上表达。神经病理学上，NHD表现出髓鞘的严重缺失和轴突球状体的积聚，伴随着在额叶和颞叶的白色物质中加重的强烈神经胶质增生。目前，NHD脑白质脑病发生的分子机制尚不清楚。通过免疫组化，我们研究了微管相关蛋白1轻链3（LC 3），自噬体标记物，在5 NHD和12个对照组的大脑中的表达。在所有NHD脑中，在非脱髓鞘白色物质中存活的Nogo-A阳性、CNPase阳性少突胶质细胞强烈表达LC 3。它们还表达泛素、泛素-1和组蛋白去乙酰化酶6（HDAC 6），但不表达Beclin 1或螯合体1（p62）。在NHD脑中，大量轴突球状体也被LC 3标记。与此相反，在对照组大脑中，少突胶质细胞均不表达LC 3。此外，位于多发性硬化（MS）脱髓鞘病变边缘的存活少突胶质细胞不表达LC 3，而浸润的Iba 1阳性巨噬细胞和小胶质细胞在MS病变中强烈表达LC 3。这些结果提出了一个新的假设，即自噬的异常调节可能会诱导少突胶质细胞病变，导致NHD脑白质脑病。
Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused by a loss-of-function mutation of either DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, dendritic cells, macrophages, and microglia. Neuropathologically, NHD exhibits profound loss of myelin and accumulation of axonal spheroids, accompanied by intense gliosis accentuated in the white matter of the frontal and temporal lobes. At present, the molecular mechanism responsible for development of leukoencephalopathy in NHD brains remains totally unknown. By immunohistochemistry, we studied the expression of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, in 5 NHD and 12 control brains. In all NHD brains, Nogo-A-positive, CNPase-positive oligodendrocytes surviving in the non-demyelinated white matter intensely expressed LC3. They also expressed ubiquitin, ubiquilin-1, and histone deacetylase 6 (HDAC6) but did not express Beclin 1 or sequestosome 1 (p62). Substantial numbers of axonal spheroids were also labeled with LC3 in NHD brains. In contrast, none of oligodendrocytes expressed LC3 in control brains. Furthermore, surviving oligodendrocytes located at the demyelinated lesion edge of multiple sclerosis (MS) did not express LC3, whereas infiltrating Iba1-positive macrophages and microglia intensely expressed LC3 in MS lesions. These results propose a novel hypothesis that aberrant regulation of autophagy might induce oligodendrogliopathy causative of leukoencephalopathy in NHD brains.
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影响因子：
64.5
作者：
Kawaguchi, Y;Kovacs, JJ;Yao, TP
通讯作者：
Yao, TP
DOI：
10.1097/01.jnen.0000248559.83573.71
发表时间：
2007-03-01
影响因子：
3.2
作者：
Kuhlmann, Tanja;Remington, Leah;Brueck, Wolfgang
通讯作者：
Brueck, Wolfgang
影响因子：
4.7
作者：
Ding, QX;Dimayuga, E;Keller, JN
通讯作者：
Keller, JN
影响因子：
4
作者：
Bianchin, MM;Capella, HM;Sakamoto, AC
通讯作者：
Sakamoto, AC
影响因子：
64.8
作者：
Lee, Youngjin;Morrison, Brett M.;Li, Yun;Lengacher, Sylvain;Farah, Mohamed H.;Hoffman, Paul N.;Liu, Yiting;Tsingalia, Akivaga;Jin, Lin;Zhang, Ping-Wu;Pellerin, Luc;Magistretti, Pierre J.;Rothstein, Jeffrey D.
通讯作者：
Rothstein, Jeffrey D.