Matrin 3 Is a Component of Neuronal Cytoplasmic Inclusions of Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis
Matrin 3 Is a Component of Neuronal Cytoplasmic Inclusions of Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis
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DOI：
10.1016/j.ajpath.2017.10.007
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发表时间：
2018-02-01
影响因子：
6
通讯作者：
Tanaka, Fumiaki
中科院分区：
文献类型：
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作者：
Tada, Mikiko;Doi, Hiroshi;Tanaka, Fumiaki
MATR 3基因突变已被确定为家族性肌萎缩侧索硬化症的原因，但matrin 3（MATR 3）蛋白在散发性肌萎缩侧索硬化症（SALS）病理中的参与尚未得到充分评估。我们化学分析了SALS和对照尸检标本脊髓中的MATR 3病理学。运动神经元核的MATR 3免疫染色显示两种不同的模式：轻度和强染色。在SALS和对照病例之间，轻度与强核染色的比率没有差异。在60%中观察到含有MATR 3的神经元胞质包涵体（NCIs）。的SALS案例。大多数运动神经元与MATR 3阳性NCI表现出轻度核染色模式。尽管估计有16.8%的反式激活反应区DNA结合蛋白43（TDP-43）阳性的NCI被MATR 3双标记，但未观察到MATR 3阳性或TDP-43阴性的NCI。尽管先前的研究发现MATR 3阳性NCI仅存在于C9 orf 72六核苷酸重复扩增的病例中，但在小脑中未观察到泛素阳性颗粒NCI，这已被报道为特异于C9 orf 72相关ALS。6例ALS病例被证实为GGGGCC六核苷酸阴性。我们的研究结果表明，MATR 3是运动神经元中TDP-43阳性NCI的组成部分，甚至在SALS中，并表明MATR 3在ALS病理学中的广泛参与和TDP-43阳性NCI的异质性。
Mutations in the MATR3 gene have been identified as a cause of familial amyotrophic lateral sclerosis, but involvement of the matrin 3 (MATR3) protein in sporadic amyotrophic lateral sclerosis (SALS) pathology has not been fully assessed. We immunohistochemically analyzed MATR3 pathology in the spinal cords of SALS and control autopsy specimens. MATR3 immunostaining of the motor neuron nuclei revealed two distinct patterns: mild and strong staining. There were no differences in the ratio of mild versus strong nuclear staining between the SALS and control cases. MATR3-containing neuronal cytoplasmic inclusions (NCIs) were observed in 60%. of SALS cases. Most motor neurons with MATR3-positive NCIs exhibited a mild nuclear staining pattern. Although 16.8% of NCIs positive for transactivating response region DNA-binding protein 43 (TDP-43) were estimated as double-Labeled by MATR3, no MATR3-positive or TDP-43-negative NCIs were observed. Although a previous study found that MATR3-positive NCIs are present only in cases with C9orf72 hexanucleotide repeat expansion, ubiquitin-positive granular NCIs were not observed in the cerebellum, which have been reported as specific to C9orf72-related ALS. Six ALS cases were confirmed to be negative for the GGGGCC hexanucleotide. Our results reveal that MATR3 is a component of TDP-43-positive NCIs in motor neurons, even in SALS, and indicate the broader involvement of MATR3 in ALS pathology and the heterogeneity of TDP-43-positive NCIs.