Department of Acupuncture and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, 210029 Nanjing, Jiangsu, China.
Front Biosci (Landmark Ed). 2023 Sep 19;28(9):208. doi: 10.31083/j.fbl2809208.
Ischemic stroke (IS) is the predominant cause of morbidity and mortality worldwide. Ferroptosis, a new type of programmed cell death, has been shown to play a crucial role in IS pathogenesis. Traditionally, research focused on neurons did not uncover specific positive results for IS. However, glial cells have recently received interest as promising targets for IS treatment, not only for their structural function but also in the iron transfer between glia and neurons, which indicates a promising glia-neuron crosstalk in mediating the IS process and ischemia/reperfusion-associated neuropathology, showing their affiliation with ferroptosis. This review addresses the major phenomena of iron metabolism and the process and regulation of ferroptosis, with a particular focus on their impact on IS pathology. The review discusses iron homeostasis, the biology of reactive oxygen species, and lipid peroxidation for modulating the process of IS-induced ferroptosis in different glial cells. We then review recent therapies that leverage ferroptosis modulation for the treatment of IS. Extensive preclinical and clinical research is necessary to fully understand the roles of glia-neuron crosstalk and ferroptosis in IS.
缺血性脑卒中（IS）是全球发病率和死亡率的主要原因。铁死亡作为一种新型的程序性细胞死亡方式，已被证明在 IS 的发病机制中起关键作用。传统上，针对神经元的研究并未发现针对 IS 的具体阳性结果。然而，胶质细胞最近作为 IS 治疗的有前途的靶点引起了关注，不仅因为它们的结构功能，还因为胶质细胞和神经元之间的铁转移，这表明在介导 IS 过程和缺血/再灌注相关神经病理学方面，胶质细胞-神经元的串扰具有很大的潜力，表明它们与铁死亡有关。本综述主要探讨了铁代谢的主要现象以及铁死亡的过程和调控，特别关注它们对 IS 病理学的影响。综述讨论了铁稳态、活性氧的生物学和脂质过氧化作用，以调节不同胶质细胞中 IS 诱导的铁死亡过程。然后，我们回顾了利用铁死亡调节治疗 IS 的最近疗法。需要进行广泛的临床前和临床研究，以充分了解胶质细胞-神经元串扰和铁死亡在 IS 中的作用。
