The cGAS−STING-mediated ROS and ferroptosis are involved in manganese neurotoxicity

IF 5.9 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Zhimin Zhang, Jirui Yang, Qiongli Zhou, Shiyin Zhong, Jingjing Liu, Xin Zhang, Xuhong Chang, Hui Wang
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引用次数: 0

Abstract

Manganese (Mn) has been characterized as an environmental pollutant. Excessive releases of Mn due to human activities have increased Mn levels in the environment over the years, posing a threat to human health and the environment. Long-term exposure to high concentrations of Mn can induce neurotoxicity. Therefore, toxicological studies on Mn are of paramount importance. Mn induces oxidative stress through affecting the level of reactive oxygen species (ROS), and the overabundance of ROS further triggers ferroptosis. Additionally, Mn2+ was found to be a novel activator of the cyclic guanosine-adenosine synthase (cGAS)−stimulator of interferon genes (STING) pathway in the innate immune system. Thus, we speculate that Mn exposure may promote ROS production by activating the cGAS−STING pathway, which further induces oxidative stress and ferroptosis, and ultimately triggers Mn neurotoxicity. This review discusses the mechanism between Mn-induced oxidative stress and ferroptosis via activation of the cGAS−STING pathway, which may offer a prospective direction for future in-depth studies on the mechanism of Mn neurotoxicity.

Abstract Image

cGAS-STING 介导的 ROS 和铁变态反应参与了锰的神经毒性作用
锰(Mn)已被定性为一种环境污染物。多年来,人类活动导致的锰过量排放增加了环境中的锰含量,对人类健康和环境构成威胁。长期接触高浓度的锰会引起神经中毒。因此,对锰进行毒理学研究至关重要。锰通过影响活性氧(ROS)的水平诱导氧化应激,而过量的 ROS 会进一步引发铁变态反应。此外,研究还发现 Mn2+ 是先天免疫系统中环鸟苷腺苷合成酶(cGAS)-干扰素基因刺激器(STING)通路的新型激活剂。因此,我们推测锰暴露可能会通过激活 cGAS-STING 通路促进 ROS 的产生,从而进一步诱导氧化应激和铁变态反应,最终引发锰神经毒性。本综述探讨了锰通过激活 cGAS-STING 通路诱导氧化应激和铁变态反应之间的机制,为今后深入研究锰的神经毒性机制提供了一个前瞻性的方向。
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来源期刊
Journal of Environmental Sciences-china
Journal of Environmental Sciences-china 环境科学-环境科学
CiteScore
13.70
自引率
0.00%
发文量
6354
审稿时长
2.6 months
期刊介绍: The Journal of Environmental Sciences is an international journal started in 1989. The journal is devoted to publish original, peer-reviewed research papers on main aspects of environmental sciences, such as environmental chemistry, environmental biology, ecology, geosciences and environmental physics. Appropriate subjects include basic and applied research on atmospheric, terrestrial and aquatic environments, pollution control and abatement technology, conservation of natural resources, environmental health and toxicology. Announcements of international environmental science meetings and other recent information are also included.
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