Jie Lu, Zhenning Wang, Zhenqiang He, Yang Hu, Hao Duan, Zihao Liu, Depei Li, Sheng Zhong, Jiaoyan Ren, Guojun Zhao, Yonggao Mou, Maojin Yao
{"title":"寡聚物Aβ42通过增强小胶质细胞的吞噬作用抑制神经胶质瘤的进展。","authors":"Jie Lu, Zhenning Wang, Zhenqiang He, Yang Hu, Hao Duan, Zihao Liu, Depei Li, Sheng Zhong, Jiaoyan Ren, Guojun Zhao, Yonggao Mou, Maojin Yao","doi":"10.1111/cns.14495","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>Glioma is characterized by an immunosuppressed environment and a poor prognosis. The accumulation of Amyloid <i>β</i> (A<i>β</i>) leads to an active environment during the early stages of Alzheimer's disease (AD). A<i>β</i> is also present in glioma tissues; however, the biological and translational implications of A<i>β</i> in glioma are elusive.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Immunohistochemical (IHC) staining, Kaplan–Meier (KM) survival analysis and Cox regression analysis on a cohort of 79 patients from our institution were performed to investigate the association between A<i>β</i> and the malignancy of glioma. Subsequently, the potential of oligomer-A<i>β</i>42 (OA<i>β</i>42) to inhibit glioma growth was investigated <i>in vivo</i> and <i>in vitro</i>. Immunofluorescence staining and phagocytosis assays were performed to evaluate the activation of microglia. Finally, RNA-seq was utilized to identify the predominant signaling involved in this process and <i>in vitro</i> studies were performed to validate them.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A positive correlation between A<i>β</i> and a favorable prognosis was observed in glioma. Furthermore, OA<i>β</i>42 suppressed glioma growth by enhancing the phagocytic activity of microglia. Insulin-like growth factor 1 (IGF-1) secreted by OA<i>β</i>42-activated microglia was essential in the engulfment process.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our study proved an anti-glioma effect of A<i>β</i>, and microglia could serve as a cellular target for treating glioma with OA<i>β</i>42.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 1","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14495","citationCount":"0","resultStr":"{\"title\":\"Oligomer-Aβ42 suppress glioma progression via potentiating phagocytosis of microglia\",\"authors\":\"Jie Lu, Zhenning Wang, Zhenqiang He, Yang Hu, Hao Duan, Zihao Liu, Depei Li, Sheng Zhong, Jiaoyan Ren, Guojun Zhao, Yonggao Mou, Maojin Yao\",\"doi\":\"10.1111/cns.14495\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Glioma is characterized by an immunosuppressed environment and a poor prognosis. The accumulation of Amyloid <i>β</i> (A<i>β</i>) leads to an active environment during the early stages of Alzheimer's disease (AD). A<i>β</i> is also present in glioma tissues; however, the biological and translational implications of A<i>β</i> in glioma are elusive.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Immunohistochemical (IHC) staining, Kaplan–Meier (KM) survival analysis and Cox regression analysis on a cohort of 79 patients from our institution were performed to investigate the association between A<i>β</i> and the malignancy of glioma. Subsequently, the potential of oligomer-A<i>β</i>42 (OA<i>β</i>42) to inhibit glioma growth was investigated <i>in vivo</i> and <i>in vitro</i>. Immunofluorescence staining and phagocytosis assays were performed to evaluate the activation of microglia. 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Oligomer-Aβ42 suppress glioma progression via potentiating phagocytosis of microglia
Aims
Glioma is characterized by an immunosuppressed environment and a poor prognosis. The accumulation of Amyloid β (Aβ) leads to an active environment during the early stages of Alzheimer's disease (AD). Aβ is also present in glioma tissues; however, the biological and translational implications of Aβ in glioma are elusive.
Methods
Immunohistochemical (IHC) staining, Kaplan–Meier (KM) survival analysis and Cox regression analysis on a cohort of 79 patients from our institution were performed to investigate the association between Aβ and the malignancy of glioma. Subsequently, the potential of oligomer-Aβ42 (OAβ42) to inhibit glioma growth was investigated in vivo and in vitro. Immunofluorescence staining and phagocytosis assays were performed to evaluate the activation of microglia. Finally, RNA-seq was utilized to identify the predominant signaling involved in this process and in vitro studies were performed to validate them.
Results
A positive correlation between Aβ and a favorable prognosis was observed in glioma. Furthermore, OAβ42 suppressed glioma growth by enhancing the phagocytic activity of microglia. Insulin-like growth factor 1 (IGF-1) secreted by OAβ42-activated microglia was essential in the engulfment process.
Conclusion
Our study proved an anti-glioma effect of Aβ, and microglia could serve as a cellular target for treating glioma with OAβ42.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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