Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?
Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?
复制标题
急性中枢神经系统损伤中的铁死亡：未来方向？
DOI：
10.3389/fcell.2020.00594
复制
发表时间：
2020-07-15
影响因子：
5.5
通讯作者：
Zhang, Jianmin
中科院分区：
文献类型：
--
作者：
Shen, Lesang;Lin, Danfeng;Zhang, Jianmin
急性中枢神经系统（CNS）损伤，例如中风、创伤性脑损伤（TBI）和脊髓损伤（SCI），由于高发病率和死亡率以及有限的临床治疗策略，在世界范围内呈现严重的卫生保健挑战。已有文献表明，氧化应激（OS）、炎症、兴奋性毒性和细胞凋亡在急性CNS损伤的病理生理过程中起重要作用。最近，有许多关于铁凋亡的研究，这是一种以铁依赖性脂质过氧化积累为特征的受调节细胞死亡形式。一些研究揭示了急性中枢神经系统损伤和铁下垂之间的联系。由脂质、谷胱甘肽（GSH）和铁代谢异常引起的铁缺乏症可加速急性中枢神经系统损伤。然而，药物制剂，如铁螯合剂，ferrostatin-1（Fer-1），和livestatin-1（Lip-1），可以抑制铁凋亡，并可能在急性中枢神经系统损伤后具有神经保护作用。然而，这种联系背后的具体机制尚未明确阐明。在本文中，我们讨论了铁凋亡的一般机制及其在中风，TBI和SCI中的作用。我们还总结了铁中毒相关的药物，并强调了潜在的治疗策略，在治疗各种急性中枢神经系统损伤。本文还提出了一个可验证的假说，即铁凋亡可能是进一步研究急性中枢神经系统损伤的一个新方向。
Acute central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI) present a grave health care challenge worldwide due to high morbidity and mortality, as well as limited clinical therapeutic strategies. Established literature has shown that oxidative stress (OS), inflammation, excitotoxicity, and apoptosis play important roles in the pathophysiological processes of acute CNS injuries. Recently, there have been many studies on the topic of ferroptosis, a form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxidation. Some studies have revealed an emerging connection between acute CNS injuries and ferroptosis. Ferroptosis, induced by the abnormal metabolism of lipids, glutathione (GSH), and iron, can accelerate acute CNS injuries. However, pharmaceutical agents, such as iron chelators, ferrostatin-1 (Fer-1), and liproxstatin-1 (Lip-1), can inhibit ferroptosis and may have neuroprotective effects after acute CNS injuries. However, the specific mechanisms underlying this connection has not yet been clearly elucidated. In this paper, we discuss the general mechanisms of ferroptosis and its role in stroke, TBI, and SCI. We also summarize ferroptosis-related drugs and highlight the potential therapeutic strategies in treating various acute CNS injuries. Additionally, this paper suggests a testable hypothesis that ferroptosis may be a novel direction for further research of acute CNS injuries by providing corresponding evidence.