Oligomer-Aβ42 suppress glioma progression via potentiating phagocytosis of microglia

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2023-10-17 DOI:10.1111/cns.14495

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

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Abstract

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.

Abstract Image

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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。

目的：胶质瘤的特点是免疫抑制环境和预后不良。淀粉样β（Aβ）的积累导致阿尔茨海默病（AD）早期的活跃环境。Aβ也存在于神经胶质瘤组织中；然而，Aβ在胶质瘤中的生物学和翻译意义尚不明确。方法：采用免疫组织化学（IHC）染色、Kaplan-Meier（KM）生存分析和Cox回归分析方法，对我院79例脑胶质瘤患者进行研究，探讨aβ与胶质瘤恶性程度的关系。随后，在体内外研究了寡聚物Aβ42（OAβ42）抑制神经胶质瘤生长的潜力。进行免疫荧光染色和吞噬作用测定以评估小胶质细胞的活化。最后，RNA-seq被用来识别参与这一过程的主要信号传导，并进行了体外研究来验证它们。结果：Aβ与胶质瘤预后呈正相关。此外，OAβ42通过增强小胶质细胞的吞噬活性来抑制神经胶质瘤的生长。OAβ42激活的小胶质细胞分泌的胰岛素样生长因子1（IGF-1）在吞噬过程中起重要作用。结论：Aβ具有抗胶质瘤作用，小胶质细胞可作为OAβ42治疗胶质瘤的细胞靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

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.