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首页> 外文期刊>Neuropathology: official journal of the Japanese Society of Neuropathology >Localization of nuclear receptor subfamily 4, group A, member 3 (NR4A3) in Lewy body disease and multiple system atrophy
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Localization of nuclear receptor subfamily 4, group A, member 3 (NR4A3) in Lewy body disease and multiple system atrophy

机译：路易氏体病和多系统萎缩中核受体亚家族4，A组，成员3（NR4A3）的定位

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摘要

Nuclear receptor subfamily 4, group A, member 3 (NR4A3), also known as neuron-derived orphan receptor-1, is a nuclear receptor which plays key roles in cell cycle, neuronal differentiation, apoptosis and metabolism. These processes may be involved in the pathogenesis of certain neurodegenerative diseases. Previous studies have shown that there are high levels of NR4A3 mRNA in the CNS. Moreover, NR4A2, a transcription factor with homology to NR4A3, has been reported to contribute to the pathogenesis of Parkinson's disease. However, it is uncertain whether NR4A3 is also involved in diseases such as dementia with Lewy bodies, multiple system atrophy, and other neurodegenerative disorders such as tauopathies, TDP-43 proteinopathies and polyglutamine diseases. In the present study we used immunohistochemistry to examine the brain and spinal cord from patients with various neurodegenerative diseases and normal control subjects using two polyclonal anti-NR4A3 antibodies. In controls, the cytoplasm of neurons and glial cells was faintly immunostained with anti-NR4A3 antibodies. In tissues from patients with neurodegenerative diseases, immunoreactivity for NR4A3 was observed in cortical and brainstem-type Lewy bodies in Parkinson's disease and in dementia with Lewy bodies, as well as in neuronal and glial cytoplasmic inclusions in multiple system atrophy. A double-labeled immunofluorescence study showed co-localization of NR4A3 and phosphorylated -synuclein in these inclusions. Neuronal and glial inclusions in other neurodegenerative disorders were NR4A3 negative. These findings suggest that accumulation of NR4A3 is specific to -synucleinopathy.
机译：核受体亚家族4，A组，成员3（NR4A3），也称为神经元孤儿受体1，是一种核受体，在细胞周期，神经元分化，细胞凋亡和代谢中起关键作用。这些过程可能与某些神经退行性疾病的发病机制有关。先前的研究表明，CNS中存在高水平的NR4A3 mRNA。此外，据报道与NR4A3具有同源性的转录因子NR4A2有助于帕金森氏病的发病。但是，尚不确定NR4A3是否也参与疾病，例如路易小体痴呆，多系统萎缩以及其他神经退行性疾病，例如陶氏病，TDP-43蛋白病和聚谷氨酰胺病。在本研究中，我们使用免疫组化技术使用两种多克隆抗NR4A3抗体检查了患有各种神经退行性疾病的患者和正常对照组的大脑和脊髓。在对照中，用抗NR4A3抗体对神经元和神经胶质细胞的细胞质进行了微弱的免疫染色。在患有神经退行性疾病的患者的组织中，在帕金森氏病的皮层和脑干型路易体中以及在路易体的痴呆症以及多系统萎缩的神经元和神经胶质细胞质包裹物中观察到NR4A3的免疫反应性。双重标记的免疫荧光研究表明，NR4A3和磷酸化突触核蛋白在这些包裹体中共定位。其他神经退行性疾病的神经元和神经胶质包涵体为NR4A3阴性。这些发现表明NR4A3的积累对-突触核蛋白病是特异性的。

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