Arginine Methylation of β-Catenin Induced by PRMT2 Aggravates LPS-Induced Cognitive Dysfunction and Depression-Like Behaviors by Promoting Ferroptosis
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
Depression is a prevalent and debilitating psychiatric disorder, imposing substantial societal and individual burdens. This study aims to investigate the involvement of ferroptosis and microglial polarization in the pathogenesis of depression, as well as the underlying mechanism. Increased protein arginine methyltransferase 2 (PRMT2) expression was observed in BV2 cells and the hippocampus following lipopolysaccharide (LPS) stimulation. Mechanistically, alkylation repair homolog protein 5 (ALKBH5)-mediated m6A modification enhanced the stability of PRMT2 mRNA. PRMT2 promoted arginine methylation of β-catenin and induced proteasomal degradation of β-catenin proteins, resulting in transcriptional inhibition of glutathione peroxidase 4 (GPX4). The upregulation of PRMT2 further accelerated microglia polarization by activating ferroptosis through the β-catenin-GPX4 axis. Depletion of PRMT2 improved LPS-induced depressive- and anxiety-like behaviors as well as cognitive impairment by inhibiting ferroptosis and M1 polarization of microglia. Our findings underscore the crucial involvement of the ALKBH5-PRMT2-β-catenin-GPX4 axis in ferroptosis and M1 polarization of microglia, thereby offering novel insights into the pathogenesis interventions for depression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Molecular neurobiology - (2024) vom: 02. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mao, Lei [VerfasserIn] |
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| Links: |
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| Themen: |
Depression |
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| Anmerkungen: |
Date Revised 02.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1007/s12035-024-04019-5 |
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NLM369202279 |
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| 245 | 1 | 0 | |a Arginine Methylation of β-Catenin Induced by PRMT2 Aggravates LPS-Induced Cognitive Dysfunction and Depression-Like Behaviors by Promoting Ferroptosis |
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| 520 | |a Depression is a prevalent and debilitating psychiatric disorder, imposing substantial societal and individual burdens. This study aims to investigate the involvement of ferroptosis and microglial polarization in the pathogenesis of depression, as well as the underlying mechanism. Increased protein arginine methyltransferase 2 (PRMT2) expression was observed in BV2 cells and the hippocampus following lipopolysaccharide (LPS) stimulation. Mechanistically, alkylation repair homolog protein 5 (ALKBH5)-mediated m6A modification enhanced the stability of PRMT2 mRNA. PRMT2 promoted arginine methylation of β-catenin and induced proteasomal degradation of β-catenin proteins, resulting in transcriptional inhibition of glutathione peroxidase 4 (GPX4). The upregulation of PRMT2 further accelerated microglia polarization by activating ferroptosis through the β-catenin-GPX4 axis. Depletion of PRMT2 improved LPS-induced depressive- and anxiety-like behaviors as well as cognitive impairment by inhibiting ferroptosis and M1 polarization of microglia. Our findings underscore the crucial involvement of the ALKBH5-PRMT2-β-catenin-GPX4 axis in ferroptosis and M1 polarization of microglia, thereby offering novel insights into the pathogenesis interventions for depression | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Microglia polarization | |
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| 650 | 4 | |a m6A modification | |
| 700 | 1 | |a You, Jiyue |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yunxia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qin |e verfasserin |4 aut | |
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