The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention.
The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention.
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DOI：
10.3390/antiox11010008
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发表时间：
2021-12-21
期刊：
影响因子：
--
通讯作者：
Cowell RM
中科院分区：
文献类型：
--
作者：
Boas SM;Joyce KL;Cowell RM
氧化应激与各种神经退行性疾病的病因学和病理学有关。在基线时，神经系统细胞有能力通过参与核因子红细胞 2 (NFE2/NRF) 依赖性转录机制来调节抗氧化防御基因，并且已经提出了许多策略来激活这些途径以促进神经保护。在这里，我们简要回顾了大脑中 NFE2/NRF 家族转录因子的生物学，并为 NFE2/NRF 家族成员在神经系统细胞中的差异细胞定位提供了证据。然后，我们在帕金森病 (PD) 和肌萎缩侧索硬化症 (ALS) 两种神经退行性疾病中观察到的氧化应激背景下讨论这些发现，并提出当前激活 NFE2/NRF 依赖性转录的策略。基于 NFE2/NRF 家族成员在有限的神经元和神经胶质细胞群中的表达，我们建议，在设计利用这些途径进行神经保护的策略时，应考虑神经元和非神经元细胞类型对组织整体氧化状态的相对贡献，以及具有最大内在产生抗氧化酶能力的细胞类型。
Oxidative stress has been implicated in the etiology and pathobiology of various neurodegenerative diseases. At baseline, the cells of the nervous system have the capability to regulate the genes for antioxidant defenses by engaging nuclear factor erythroid 2 (NFE2/NRF)-dependent transcriptional mechanisms, and a number of strategies have been proposed to activate these pathways to promote neuroprotection. Here, we briefly review the biology of the transcription factors of the NFE2/NRF family in the brain and provide evidence for the differential cellular localization of NFE2/NRF family members in the cells of the nervous system. We then discuss these findings in the context of the oxidative stress observed in two neurodegenerative diseases, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), and present current strategies for activating NFE2/NRF-dependent transcription. Based on the expression of the NFE2/NRF family members in restricted populations of neurons and glia, we propose that, when designing strategies to engage these pathways for neuroprotection, the relative contributions of neuronal and non-neuronal cell types to the overall oxidative state of tissue should be considered, as well as the cell types which have the greatest intrinsic capacity for producing antioxidant enzymes.
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