دورية أكاديمية
RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation.
| العنوان: | RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation. |
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| المؤلفون: | Hu W; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Electronic address: fcchuwt@zzu.edu.cn., Wang M; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China., Sun G; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China., Zhang L; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China., Lu H; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Electronic address: zzu_luhong@163.com. |
| المصدر: | Experimental cell research [Exp Cell Res] 2024 Jun 01; Vol. 439 (1), pp. 114088. Date of Electronic Publication: 2024 May 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0373226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2422 (Electronic) Linking ISSN: 00144827 NLM ISO Abbreviation: Exp Cell Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Orlando Fl : Academic Press Original Publication: New York, Academic Press. |
| مواضيع طبية MeSH: | Microglia*/metabolism , Microglia*/pathology , NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein*/genetics , Inflammasomes*/metabolism , rho GTP-Binding Proteins*/metabolism , rho GTP-Binding Proteins*/genetics , Mice, Inbred C57BL* , Parkinson Disease*/metabolism , Parkinson Disease*/pathology , Parkinson Disease*/genetics, Animals ; Mice ; Male ; Neuroinflammatory Diseases/metabolism ; Neuroinflammatory Diseases/pathology ; Lipopolysaccharides/pharmacology ; Disease Models, Animal ; Cell Polarity ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation/genetics ; Interferon-gamma/metabolism |
| مستخلص: | Neuroinflammation mediated by microglia plays an important role in the etiology of Parkinson's disease (PD). Rho family GTPase 3 (RND3) exerts anti-inflammatory effects and may act as a potential new inducer of neuroprotective phenotypes in microglia. However, whether RND3 can be used to regulate microglia activation or reduce neuroinflammation in PD remains elusive. The study investigated the microglia modulating effects and potential anti-inflammatory effects of RND3 in vivo and in vitro, using animal models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and cell models of BV-2 cells stimulated by LPS plus IFN-γ with or without RND3-overexpression. The results showed that RND3 was highly expressed in the MPTP-induced PD mouse model and BV-2 cells treated with LPS and IFN-γ. In vivo experiments confirmed that RND3 overexpression could modulate microglia phenotype and ameliorate MPTP-induced neuroinflammation through inhibiting activation of the NLRP3 inflammasome in substantia nigra pars compacta (SNpc). In vitro study showed that RND3 overexpression could attenuate the production of pro-inflammatory factors in BV2 cells stimulated by LPS and IFN-γ. Mechanistically, RND3 reduced the activation of the NLRP3 inflammasome upon LPS and IFN-γ stimulation. Taken together, these findings suggest that RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation. Competing Interests: Declaration of competing interest The authors declare no conflict of interest. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Microglia activation; NLRP3 inflammasome; Parkinson's disease; RND3 |
| المشرفين على المادة: | 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (Inflammasomes) EC 3.6.5.2 (rho GTP-Binding Proteins) EC 3.6.1.- (Rnd3 protein, mouse) 0 (Nlrp3 protein, mouse) 0 (Lipopolysaccharides) 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) 82115-62-6 (Interferon-gamma) |
| تواريخ الأحداث: | Date Created: 20240514 Date Completed: 20240605 Latest Revision: 20240613 |
| رمز التحديث: | 20240613 |
| DOI: | 10.1016/j.yexcr.2024.114088 |
| PMID: | 38744409 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2422 |
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| DOI: | 10.1016/j.yexcr.2024.114088 |