Moubarak Maya M, Pagano Zottola Antonio C, Larrieu Claire M, Cuvellier Sylvain, Daubon Thomas, Martin Océane C B
University of Bordeaux, CNRS, IBGC, UMR 5095, Bordeaux, France.
Neurooncol Adv. 2023 Dec 23;6(1):vdad160. doi: 10.1093/noajnl/vdad160. eCollection 2024 Jan-Dec.
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. 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 4 glioma, tumor resistance, and recurrence are caused by the glioblastoma stem cell 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.
由于大脑对氧气的利用率高以及伴随产生的活性氧，慢性氧化应激在脑恶性肿瘤的发展中起关键作用。核因子红细胞2相关因子2（NRF2）作为抗氧化信号的主要调节因子，是调节大脑生理和年龄相关性神经退行性疾病发展的关键因素。此外，已知NRF2通过调节各种信号通路和下游靶基因，在发挥促癌活性的同时，对包括癌症在内的氧化应激诱导疾病的发生具有保护性抗氧化作用。在胶质母细胞瘤（GB），即4级胶质瘤中，肿瘤耐药性和复发是由构成肿瘤核心一小部分的胶质母细胞瘤干细胞群体引起的。GB组织中NRF2的表达增强了这些细胞群体的持久性和自我更新能力。本综述概述了NRF2在癌症中的双重作用，突出了其在人类大脑生理和疾病中的调节作用，以及原发性脑肿瘤的发展和治疗潜力，重点是GB。
