RBM5 induces motor neuron apoptosis in hSOD1G93A-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways

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<sup>G93A</sup>-NSC34 cell models and hSOD1<sup>G93A</sup> 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<sup>G93A</sup>-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.

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Publication Details

Journal
Brain Research Bulletin
Published
2024-08-12
DOI
https://doi.org/10.1016/j.brainresbull.2024.111049
Primary Topic
Amyotrophic Lateral Sclerosis Research
Type
article
Field-Weighted Citation Impact
0.00

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article

RBM5 induces motor neuron apoptosis in hSOD1G93A-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways

Wenmo Zhang, Hongyong Wang, Xingli Tan, Jing Xu et al.
Brain Research Bulletin
Amyotrophic Lateral Sclerosis Research
article

RBM5 induces motor neuron apoptosis in hSOD1G93A-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways

Wenmo Zhang, Hongyong Wang, Xingli Tan, Jing Xu, Di Huo, Weiwei Liang, Honglin Feng, Dongmei Zhang, Ying Wang, Di Wang, Ming Wang, Qi Yan, Xiaoli Su, Ling Han
article en

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 hSOD1<sup>G93A</sup>-NSC34 cell models and hSOD1<sup>G93A</sup> 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<sup>G93A</sup>-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.

Brain Research BulletinVol. 216
Harbin Medical University (CN), Shanxi Medical University (CN), Second Affiliated Hospital of Harbin Medical University (CN), Second Hospital of Shanxi Medical University (CN), First Affiliated Hospital of Harbin Medical University (CN)
National Natural Science Foundation of China
Openalex Percentile: Top 80%
Amyotrophic Lateral Sclerosis Research
DOIOpen Access PDFOpenAlex
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