Abstract：
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by gradual depletion of motor neurons. RNA binding motif protein 5 (RBM5), an abundantly expressed RNA-binding protein, plays a critical role in the process of cellular death. However, little is known about the role of RBM5 in the pathogenesis of ALS. Here, we found that RBM5 was upregulated in ALS hSOD1G93A-NSC34 cell models and hSOD1G93A mice due to a reduction of miR-141-5p. The upregulation of RBM5 increased the apoptosis of motor neurons by inhibiting Rac1-mediated neuroprotection. In contrast, genetic knockdown of RBM5 rescued motor neurons from hSOD1G93A-induced degeneration by activating Rac1 signaling. The neuroprotective effect of RBM5-knockdown was significantly inhibited by the Rac1 inhibitor, NSC23766. These findings suggest that RBM5 could potentially serve as a therapeutic target in ALS by activating the Rac1 signalling.
摘要：
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是运动神经元逐渐耗尽。RNA结合基序蛋白5（RBM5），一种大量表达的RNA结合蛋白，在细胞死亡过程中起着至关重要的作用。然而,关于RBM5在ALS发病机制中的作用知之甚少。这里,我们发现,由于miR-141-5p的减少,RBM5在ALShSOD1G93A-NSC34细胞模型和hSOD1G93A小鼠中上调.RBM5的上调通过抑制Rac1介导的神经保护作用增加了运动神经元的凋亡。相比之下,RBM5的基因敲除通过激活Rac1信号从hSOD1G93A诱导的变性中拯救了运动神经元。Rac1抑制剂显著抑制RBM5敲低的神经保护作用,NSC23766。这些发现表明RBM5可能通过激活Rac1信号传导作为ALS的治疗靶标。
