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Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia
Background: Neuroinflammation is involved in the development of Parkinson's disease (PD). Calhm2 plays an important role in the development of microglial inflammation, but whether Calhm2 is involved in PD and its regulatory mechanisms are unclear. Methods: To study the role of Calhm2 in the dev...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091876/ https://www.ncbi.nlm.nih.gov/pubmed/37064868 http://dx.doi.org/10.7150/thno.83082 |
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author | Bo, Xuena Xie, Fei Zhang, Jingdan Gu, Runze Li, Xiaoheng Li, Shuoshuo Yuan, Zengqiang Cheng, Jinbo |
author_facet | Bo, Xuena Xie, Fei Zhang, Jingdan Gu, Runze Li, Xiaoheng Li, Shuoshuo Yuan, Zengqiang Cheng, Jinbo |
author_sort | Bo, Xuena |
collection | PubMed |
description | Background: Neuroinflammation is involved in the development of Parkinson's disease (PD). Calhm2 plays an important role in the development of microglial inflammation, but whether Calhm2 is involved in PD and its regulatory mechanisms are unclear. Methods: To study the role of Calhm2 in the development of PD, we utilized conventional Calhm2 knockout mice, microglial Calhm2 knockout mice and neuronal Calhm2 knockout mice, and established the MPTP-induced PD mice model. Moreover, a series of methods including behavioral test, immunohistochemistry, immunofluorescence, real-time polymerase chain reaction, western blot, mass spectrometry analysis and co-immunoprecipitation were utilized to study the regulatory mechanisms. Results: We found that both conventional Calhm2 knockout and microglial Calhm2 knockout significantly reduced dopaminergic neuronal loss, and decreased microglial numbers, thereby improving locomotor performance in PD model mice. Mechanistically, we found that Calhm2 interacted with EFhd2 and regulated downstream STAT3 signaling in microglia. Knockdown of Calhm2 or EFhd2 both inhibited downstream STAT3 signaling and inflammatory cytokine levels in microglia. Conclusion: We demonstrate the important role of Calhm2 in microglial activation and the pathology of PD, thus providing a potential therapeutic target for microglia-mediated neuroinflammation-related diseases. |
format | Online Article Text |
id | pubmed-10091876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-100918762023-04-13 Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia Bo, Xuena Xie, Fei Zhang, Jingdan Gu, Runze Li, Xiaoheng Li, Shuoshuo Yuan, Zengqiang Cheng, Jinbo Theranostics Research Paper Background: Neuroinflammation is involved in the development of Parkinson's disease (PD). Calhm2 plays an important role in the development of microglial inflammation, but whether Calhm2 is involved in PD and its regulatory mechanisms are unclear. Methods: To study the role of Calhm2 in the development of PD, we utilized conventional Calhm2 knockout mice, microglial Calhm2 knockout mice and neuronal Calhm2 knockout mice, and established the MPTP-induced PD mice model. Moreover, a series of methods including behavioral test, immunohistochemistry, immunofluorescence, real-time polymerase chain reaction, western blot, mass spectrometry analysis and co-immunoprecipitation were utilized to study the regulatory mechanisms. Results: We found that both conventional Calhm2 knockout and microglial Calhm2 knockout significantly reduced dopaminergic neuronal loss, and decreased microglial numbers, thereby improving locomotor performance in PD model mice. Mechanistically, we found that Calhm2 interacted with EFhd2 and regulated downstream STAT3 signaling in microglia. Knockdown of Calhm2 or EFhd2 both inhibited downstream STAT3 signaling and inflammatory cytokine levels in microglia. Conclusion: We demonstrate the important role of Calhm2 in microglial activation and the pathology of PD, thus providing a potential therapeutic target for microglia-mediated neuroinflammation-related diseases. Ivyspring International Publisher 2023-03-13 /pmc/articles/PMC10091876/ /pubmed/37064868 http://dx.doi.org/10.7150/thno.83082 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Bo, Xuena Xie, Fei Zhang, Jingdan Gu, Runze Li, Xiaoheng Li, Shuoshuo Yuan, Zengqiang Cheng, Jinbo Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia |
title | Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia |
title_full | Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia |
title_fullStr | Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia |
title_full_unstemmed | Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia |
title_short | Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia |
title_sort | deletion of calhm2 alleviates mptp-induced parkinson's disease pathology by inhibiting efhd2-stat3 signaling in microglia |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091876/ https://www.ncbi.nlm.nih.gov/pubmed/37064868 http://dx.doi.org/10.7150/thno.83082 |
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