Early and selective reduction of NOP56 (Asidan) and RNA processing proteins in the motor neuron of ALS model mice
Early and selective reduction of NOP56 (Asidan) and RNA processing proteins in the motor neuron of ALS model mice
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DOI：
10.1179/1743132813y.0000000196
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发表时间：
2013-09
影响因子：
1.9
通讯作者：
K. Miyazaki;T. Yamashita;N. Morimoto;Kota Sato;Takafumi Mimoto;T. Kurata;Y. Ikeda;K. Abe
中科院分区：
文献类型：
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作者：
K. Miyazaki;T. Yamashita;N. Morimoto;Kota Sato;Takafumi Mimoto;T. Kurata;Y. Ikeda;K. Abe
摘要目的：越来越多的证据支持RNA加工改变与肌萎缩侧索硬化症（ALS）运动神经元变性的发病机制有关。在本研究中，我们评估了三种RNA加工相关蛋白在ALS模型小鼠中的表达。方法：分析转基因（Tg） SOD1 G93A ALS模型小鼠运动神经元退行性变过程中三种RNA加工相关蛋白的表达和分布模式，核核蛋白（NOP） 56（被鉴定为脊髓小脑共济失调（SCA） 36的致病基因）、TDP-43和融合在肉瘤/易位脂肪肉瘤（FUS）中的表达和分布模式，这些肉瘤位于腰椎和颈索、口下核、大脑运动皮层和小脑。结果：与年龄匹配野生型（WT）小鼠相比，Tg小鼠从症状早期（14周龄）到疾病末期（18周龄），腰颈索大运动神经元中NOP56水平渐进式降低。大运动神经元核中TDP-43和FUS蛋白水平在18周（疾病末期）后下降。在大脑初级运动皮层、小脑的分子层和颗粒层以及浦肯野细胞中没有观察到这些变化。讨论：目前的研究表明，这三种核蛋白的逐渐丢失和随后的RNA加工问题，包括一个与ALS相关的新基因（NOP56）在运动神经元变性下。
Abstract Objective: There is increasing evidence to support that altered RNA processing is implicated in the pathogenesis of motor neuron degeneration of amyotrophic lateral sclerosis (ALS). We evaluate the expression of three RNA processing-related proteins in ALS model mice in this study. Methods: We analyzed expression and distribution patterns of three RNA processing-related proteins, nucleolar protein (NOP) 56 (identified as causative gene for spinocerebellar ataxia (SCA) 36, nicknamed Asidan), TDP-43, and fused in sarcoma/translocated in liposarcoma (FUS) in lumbar and cervical cords, hypoglossal nucleus, cerebral motor cortex, and cerebellum of transgenic (Tg) SOD1 G93A ALS model mice throughout the course of motor neuron degeneration. Results: Compared to age-matched wild type (WT) mice, Tg mice showed progressive reduction of NOP56 levels in the large motor neurons of lumbar and cervical cords from the early-symptomatic stage (14 weeks of age) to the end stage of the disease (18 weeks). TDP-43 and FUS protein levels showed a later decrease in the nucleus of large motor neuron at 18 weeks (end stage of the disease). These changes were not observed in the primary motor cortex of the cerebrum as well as molecular and granular layers and Purkinje cells in the cerebellum. Discussion: The present study suggests a progressive loss of these three nuclear proteins and subsequent RNA processing problems including a novel gene relating to ALS (NOP56) under the motor neuron degeneration.