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胶质母细胞瘤中铁死亡的分子机制及铁死亡信号通路的潜在治疗靶点

Molecular mechanisms of ferroptosis and the potential therapeutic targets of ferroptosis signaling pathways for glioblastoma.

作者信息

Zhang Meng, Lei Qian, Huang Xiaobo, Wang Yi

机构信息

Department of Anesthesiology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Department of Critical Care Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

出版信息

Front Pharmacol. 2022 Nov 24;13:1071897. doi: 10.3389/fphar.2022.1071897. eCollection 2022.

Abstract

Ferroptosis is a newly identified form of cell death that differs from autophagy, apoptosis and necrosis, and its molecular characteristics include iron-dependent lipid reactive oxygen species accumulation, mitochondrial morphology changes, and membrane permeability damage. These characteristics are closely related to various human diseases, especially tumors of the nervous system. Glioblastoma is the most common primary malignant tumor of the adult central nervous system, and the 5-year survival rate is only 4%-5%. This study reviewed the role and mechanism of ferroptosis in glioblastoma and the research status and progress on ferroptosis as a potential therapeutic target. The mechanism of ferroptosis is related to the intracellular iron metabolism level, lipid peroxide content and glutathione peroxidase 4 activity. It is worth exploring how ferroptosis can be applied in disease treatment; however, the relation between ferroptosis and other apoptosis methods is poorly understood and methods of applying ferroptosis to drug-resistant tumors are insufficient. Ferroptosis is a promising therapeutic target for glioblastoma. In-depth studies of its mechanism of action in glioblastoma and applications for clinical treatment are expected to provide insights for glioblastoma patients.

摘要

铁死亡是一种新发现的细胞死亡形式,不同于自噬、凋亡和坏死,其分子特征包括铁依赖性脂质活性氧积累、线粒体形态变化和膜通透性损伤。这些特征与多种人类疾病密切相关,尤其是神经系统肿瘤。胶质母细胞瘤是成人中枢神经系统最常见的原发性恶性肿瘤,5年生存率仅为4%-5%。本研究综述了铁死亡在胶质母细胞瘤中的作用和机制,以及铁死亡作为潜在治疗靶点的研究现状和进展。铁死亡的机制与细胞内铁代谢水平、脂质过氧化物含量和谷胱甘肽过氧化物酶4活性有关。值得探讨如何将铁死亡应用于疾病治疗;然而,铁死亡与其他凋亡方法之间的关系尚不清楚,将铁死亡应用于耐药肿瘤的方法也不足。铁死亡是胶质母细胞瘤一个有前景的治疗靶点。深入研究其在胶质母细胞瘤中的作用机制并应用于临床治疗,有望为胶质母细胞瘤患者提供新的治疗思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e701/9729877/c01abc8b5ada/fphar-13-1071897-g001.jpg

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