Centre for Research in Neuroscience, and BRaIN Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.
Neuroscientist. 2023 Oct;29(5):591-615. doi: 10.1177/10738584221100183. Epub 2022 Jun 8.
Iron accumulation in the CNS occurs in many neurological disorders. It can contribute to neuropathology as iron is a redox-active metal that can generate free radicals. The reasons for the iron buildup in these conditions are varied and depend on which aspects of iron influx, efflux, or sequestration that help maintain iron homeostasis are dysregulated. Iron was shown recently to induce cell death and damage via lipid peroxidation under conditions in which there is deficient glutathione-dependent antioxidant defense. This form of cell death is called . Iron chelation has had limited success in the treatment of neurological disease. There is therefore much interest in ferroptosis as it potentially offers new drugs that could be more effective in reducing iron-mediated lipid peroxidation within the lipid-rich environment of the CNS. In this review, we focus on the molecular mechanisms that induce ferroptosis. We also address how iron enters and leaves the CNS, as well as the evidence for ferroptosis in several neurological disorders. Finally, we highlight biomarkers of ferroptosis and potential therapeutic strategies.
铁在中枢神经系统中的积累发生在许多神经疾病中。铁是一种具有氧化还原活性的金属，可以产生自由基，因此它会导致神经病理学。在这些情况下，铁的积累的原因是多种多样的，这取决于哪些方面的铁内流、外流或隔离有助于维持铁的体内平衡被打乱。最近的研究表明，在谷胱甘肽依赖的抗氧化防御功能不足的情况下，铁通过脂质过氧化诱导细胞死亡和损伤。这种形式的细胞死亡称为铁死亡。铁螯合在神经疾病的治疗中仅取得了有限的成功。因此，人们对铁死亡产生了浓厚的兴趣，因为它可能提供新的药物，在富含脂质的中枢神经系统环境中，这些药物在减少铁介导的脂质过氧化方面可能更有效。在这篇综述中，我们重点介绍诱导铁死亡的分子机制。我们还讨论了铁如何进入和离开中枢神经系统，以及在几种神经疾病中存在铁死亡的证据。最后，我们强调了铁死亡的生物标志物和潜在的治疗策略。
