Wang Hailing, Jia Liwei, Yin Rui, Xu Shujun, Meng Xin
School of Pharmacy, Heilongjiang University of Chinese Medicine, NO. 24 Heping Road, Harbin, 150040, People's Republic of China.
J Mol Neurosci. 2025 Jun 14;75(2):76. doi: 10.1007/s12031-025-02369-w.
Ferroptosis, a distinct form of cell death, is transforming the understanding of complex diseases such as cancer, neurodegenerative disorders. Driven by iron accumulation and lipid peroxidation, ferroptosis offers significant therapeutic potential by selectively targeting diseased cells. Ferroptosis is closely associated with renal impairment, metabolic disease, and neurological disorders. The current focus is on understanding the signaling pathways of ferroptosis to precisely regulate the ferroptosis mechanism. For example, ferroptosis increases intracellular selenium content and synergistically activates transcription factors transcription factor AP-2 gamma and specificity protein 1 to promote glutathione peroxidase-4 expression (GPX4). Despite its broad therapeutic potential, significant challenges remain, particularly in uncovering the detailed molecular mechanisms of ferroptosis and minimizing off-target effects. However, in the past two years, there has been a few comprehensive reviews on the exploration of therapeutic targets related to ferroptosis in disease treatment. This article provides a summary of the current understanding of ferroptosis mechanisms, its links to various diseases, and the exploration of potential therapeutic targets. By elucidating the complex molecular pathways of ferroptosis and highlighting its role in disease progression, we gain new insights for potential therapeutic strategies. This underscores the substantial theoretical significance of targeting ferroptosis for treatment purposes.
铁死亡是一种独特的细胞死亡形式，正在改变人们对癌症、神经退行性疾病等复杂疾病的理解。在铁积累和脂质过氧化的驱动下，铁死亡通过选择性地靶向病变细胞具有显著的治疗潜力。铁死亡与肾功能损害、代谢疾病和神经疾病密切相关。当前的重点是了解铁死亡的信号通路，以精确调控铁死亡机制。例如，铁死亡会增加细胞内硒含量，并协同激活转录因子转录因子AP-2γ和特异性蛋白1，以促进谷胱甘肽过氧化物酶4（GPX4）的表达。尽管其具有广泛的治疗潜力，但仍存在重大挑战，特别是在揭示铁死亡的详细分子机制和尽量减少脱靶效应方面。然而，在过去两年中，关于在疾病治疗中探索与铁死亡相关的治疗靶点已有一些全面的综述。本文总结了目前对铁死亡机制的理解、其与各种疾病的联系以及对潜在治疗靶点的探索。通过阐明铁死亡的复杂分子途径并突出其在疾病进展中的作用，我们为潜在的治疗策略获得了新的见解。这凸显了以铁死亡为靶点进行治疗的重大理论意义。
