CNS neuroscience & therapeutics · 2023
Oligomer-Aβ42 suppress glioma progression via potentiating phagocytosis of microglia.
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Lu Jie, Wang Zhenning, He Zhenqiang, Hu Yang, Duan Hao, Liu Zihao, Li Depei, Zhong Sheng, Ren Jiaoyan, Zhao Guojun, Mou Yonggao, Yao Maojin
Аннотация
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.
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.