Oligomer-Aβ42 suppress glioma progression via potentiating phagocytosis of microglia

作者：Lu, Jie; Wang, Zhenning; He, Zhenqiang; Hu, Yang; Duan, Hao; Liu, Zihao; Li, Depei; Zhong, Sheng; Ren, Jiaoyan; Zhao, Guojun^*; Mou, Yonggao^*; Yao, Maojin^*

来源：CNS Neuroscience & Therapeutics, 2024, 30(1).

DOI：10.1111/cns.14495

• glioma
• IGF-1
• microglia
• OA beta 42
• phagocytosis

Aims: Glioma is characterized by an immunosuppressed environment and a poor prognosis. The accumulation of Amyloid beta (A beta) leads to an active environment during the early stages of Alzheimer's disease (AD). A beta is also present in glioma tissues; however, the biological and translational implications of A beta 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 A beta and the malignancy of glioma. Subsequently, the potential of oligomer-A beta 42 (OA beta 42) 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 A beta and a favorable prognosis was observed in glioma. Furthermore, OA beta 42 suppressed glioma growth by enhancing the phagocytic activity of microglia. Insulin-like growth factor 1 (IGF-1) secreted by OA beta 42-activated microglia was essential in the engulfment process.Conclusion: Our study proved an anti-glioma effect of A beta, and microglia could serve as a cellular target for treating glioma with OA beta 42.

• 单位
  广州医学院; 1; 南方医科大学; 6; 东莞市人民医院; 中山大学