https://doi.org/10.1016/j.apsb.2025.06.005
This new article publication from
Acta Pharmaceutica Sinica B, discusses how the protein arginine methyltransferase PRMT1 ameliorates cerebral ischemia–reperfusion injury by suppressing RIPK1-mediated necroptosis and apoptosis.
Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. The authors of this article found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, it was proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. These findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.
Keywords: PRMT1, Cerebral ischemia–reperfusion injury, RIPK1, Phosphorylation, Arginine methylation, Necroptosis, Apoptosis, MLKL
Graphical Abstract: available at
https://ars.els-cdn.com/content/image/1-s2.0-S2211383525004083-ga1_lrg.jpg
In cerebral ischemia–reperfusion injury, the downregulation of PRMT1 activated RIPK1 in neurons by reducing its methylation, which ultimately exacerbated RIPK1-mediated necroptosis and apoptosis.
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The Journal of the
Institute of Materia Medica, the Chinese Academy of Medical Sciences and the
Chinese Pharmaceutical Association.
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CiteScore: 24.3
Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 13.8
ISSN 2211-3835
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Tengfei Liu, Gan Huang, Xin Guo, Qiuran Ji, Lu Yu, Runzhe Zong, Yiquan Li, Xiaomeng Song, Qingyi Fu, Qidi Xue, Yi Zheng, Fanshuo Zeng, Ru Sun, Lin Chen, Chengjiang Gao, Huiqing Liu, The protein arginine methyltransferase PRMT1 ameliorates cerebral ischemia–reperfusion injury by suppressing RIPK1-mediated necroptosis and apoptosis, Acta Pharmaceutica Sinica B, Volume 15, Issue 8, 2025, Pages 4014-4029, ISSN 2211-3835,
https://doi.org/10.1016/j.apsb.2025.06.005