GSK-3β, a double-edged sword in Nrf2 regulation: Implications for neurological dysfunction and disease.
GSK-3β, a double-edged sword in Nrf2 regulation: Implications for neurological dysfunction and disease.
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DOI：
10.12688/f1000research.15239.1
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Aschner M
中科院分区：
文献类型：
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作者：
Culbreth M;Aschner M
在过去的十年中，糖原合成酶激酶3β（GSK-3β）调节核因子红细胞2相关因子2（Nrf 2）氧化应激反应的研究已变得越来越明显。GSK-3β在Nrf 2的激活和诱导后的间接作用中直接起抑制剂的作用。氧化应激在神经功能障碍和疾病中的发生率使得该信号通路成为有吸引力的治疗靶点。然而，除了典型的氧化应激反应外，几乎没有证据支持GSK-3β介导的Nrf 2抑制在神经系统衰退中的独特功能。在阿尔茨海默病和脑缺血中，已经探索了该途径对疾病病因学和进展的潜在益处。目前，尚不清楚GSK-3β介导的Nrf 2抑制是否显著影响这些疾病状态。此外，每一种在神经退行性衰退中具有独特功能的可能性是未经证实的。
In the past decade, it has become evident that glycogen synthase kinase 3β (GSK-3β) modulates the nuclear factor erythroid 2-related factor 2 (Nrf2) oxidative stress response. GSK-3β functions as an inhibitor, both directly in the activation and indirectly in the post-induction of Nrf2. The incidence of oxidative stress in neurological dysfunction and disease has made this signaling pathway an attractive therapeutic target. There is minimal evidence, however, to support a distinctive function for GSK-3β mediated Nrf2 inhibition in nervous system decline, apart from the typical oxidative stress response. In both Alzheimer’s disease and brain ischemia, this pathway has been explored for potential benefits on disease etiology and advancement. Presently, it is unclear whether GSK-3β mediated Nrf2 inhibition markedly influences these disease states. Furthermore, the potential that each has unique function in neurodegenerative decline is unsubstantiated.