Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
Mol Neurobiol. 2018 Feb;55(2):1323-1337. doi: 10.1007/s12035-017-0406-9. Epub 2017 Jan 26.
The known proteins only explained the partial pathogenesis of amyotrophic lateral sclerosis (ALS). Therefore, this study aimed to search the novel proteins possibly involved in ALS. In this study, we analyzed the expression and distribution of the candidate protein arylsulfatase B (ARSB) in the different segments, anatomic regions, and neural cells of spinal cord at the different stages of the wild-type and [Cu/Zn] superoxide dismutase 1 (SOD1) G93A transgenic mice using the fluorescent immunohistochemistry and the western blot. The results revealed that the ARSB was extensively expressed and distributed in the entire spinal cord; the expression and distribution of ARSB was significantly different in the different regions of spinal cord, the anterior horn of gray matter (AHGM) was significantly more than that in the posterior horn of gray matter (PHGM) and significantly more than that in the central canal, and ARSB was mainly distributed in the microglia and neuron cells in the wild-type mice. The expression of ARSB significantly increased in other anatomic regions besides the thoracic PHGM, significantly decreased at the progression stage, occurred in the redistribution from the AHGM and the PHGM to the central canal at the onset and progression stages, and no any alteration of ARSB expression and distribution occurred between the different neural cells in the SOD1 G93A mice compared with the wild-type mice. The increase of ARSB expression and distribution followed with the increased of neuron death. Our data suggested that the abnormal expression and distribution of ARSB were closely associated with the neuron death in the SOD1 G93A transgenic mice.
已知的蛋白质仅解释了部分肌萎缩侧索硬化症(ALS)的发病机制。因此,本研究旨在寻找可能与 ALS 相关的新型蛋白质。在这项研究中,我们使用荧光免疫组织化学和 Western blot 分析了野生型和 [Cu/Zn] 超氧化物歧化酶 1(SOD1)G93A 转基因小鼠不同阶段脊髓不同节段、解剖区域和神经细胞中候选蛋白芳基硫酸酯酶 B(ARSB)的表达和分布。结果表明,ARSB 在整个脊髓中广泛表达和分布;ARSB 在脊髓不同区域的表达和分布存在显著差异,灰质前角(AHGM)明显多于灰质后角(PHGM),明显多于中央管,ARSB 主要分布在野生型小鼠的小胶质细胞和神经元细胞中。在除胸 PHGM 以外的其他解剖区域,ARSB 的表达显著增加,在进展阶段显著降低,在发病和进展阶段从 AHGM 和 PHGM 向中央管重新分布,与野生型小鼠相比,SOD1 G93A 小鼠中不同神经细胞之间的 ARSB 表达和分布没有任何变化。ARSB 表达和分布的增加伴随着神经元死亡的增加。我们的数据表明,ARSB 的异常表达和分布与 SOD1 G93A 转基因小鼠中的神经元死亡密切相关。