Exploring the Multifaceted Role of NRF2 in Brain Physiology and Cancer: A Comprehensive Review

Neuro-oncology Advances Pub Date : 2023-12-23 DOI:10.1093/noajnl/vdad160

Maya M Moubarak, Antonio C Pagano Zottola, Claire M Larrieu, Sylvain Cuvellier, T. Daubon, O. C. Martin

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Abstract

Chronic oxidative stress plays a critical role in the development of brain malignancies due to the high rate of brain oxygen utilization and concomitant production of reactive oxygen species (ROS). The nuclear factor-erythroid-2-related factor 2 (NRF2), a master regulator of antioxidant signaling, is a key factor in regulating brain physiology and the development of age-related neurodegenerative diseases. Also, NRF2 is known to exert a protective antioxidant effect against the onset of oxidative stress-induced diseases, including cancer, along with its pro-oncogenic activities through regulating various signaling pathways and downstream target genes. In glioblastoma (GB), grade IV glioma, tumor resistance, and recurrence are caused by the glioblastoma stem cell (GSC) population constituting a small bulk of the tumor core. The persistence and self-renewal capacity of these cell populations is enhanced by NRF2 expression in GB tissues. This review outlines NRF2's dual involvement in cancer and highlights its regulatory role in human brain physiology and diseases, in addition to the development of primary brain tumors and therapeutic potential, with a focus on GB.

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探索 NRF2 在脑生理学和癌症中的多方面作用：全面回顾

慢性氧化应激在脑部恶性肿瘤的发展过程中起着至关重要的作用，因为脑部氧气利用率高，同时会产生活性氧（ROS）。核因子-红细胞-2 相关因子 2（NRF2）是抗氧化信号转导的主要调节因子，是调节大脑生理机能和与年龄相关的神经退行性疾病发展的关键因素。此外，NRF2 还通过调节各种信号通路和下游靶基因，对氧化应激诱发的疾病（包括癌症）发挥抗氧化保护作用，并具有促癌活性。在胶质母细胞瘤（GB）、IV 级胶质瘤中，肿瘤耐药性和复发是由占肿瘤核心一小部分的胶质母细胞瘤干细胞（GSC）群体引起的。GB 组织中 NRF2 的表达增强了这些细胞群的持续存在和自我更新能力。本综述概述了 NRF2 在癌症中的双重参与，强调了它在人类脑部生理和疾病中的调控作用，以及原发性脑肿瘤的发展和治疗潜力，重点关注 GB。

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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Neuro-oncology Advances

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