RBM5 通过抑制 Rac1/AKT 通路诱导与 hSOD1 相关的肌萎缩侧索硬化症运动神经元凋亡。
RBM5 induces motor neuron apoptosis in hSOD1-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways.
机构信息
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150000, China; Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
出版信息
Brain Res Bull. 2024 Oct 1;216:111049. doi: 10.1016/j.brainresbull.2024.111049. Epub 2024 Aug 12.
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 hSOD1-NSC34 cell models and hSOD1 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 hSOD1-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.
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竭。RNA 结合基序蛋白 5（RBM5）是一种大量表达的 RNA 结合蛋白，在细胞死亡过程中发挥关键作用。然而，RBM5 在 ALS 发病机制中的作用知之甚少。在这里，我们发现由于 miR-141-5p 的减少，RBM5 在 ALS hSOD1-NSC34 细胞模型和 hSOD1 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运动神经元的凋亡。相比之下，通过激活 Rac1 信号，RBM5 的基因敲低可挽救 hSOD1 诱导的运动神经元退化。Rac1 抑制剂 NSC23766 显著抑制了 RBM5 敲低的神经保护作用。这些发现表明，通过激活 Rac1 信号，RBM5 有可能成为 ALS 的治疗靶点。
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