铁死亡调控神经退行性疾病及多器官损伤的机制与靶向干预研究进展

doi:10.6040/j.issn.1671-7554.0.2026.1236

摘要/Abstract

摘要： 铁死亡是一种铁离子依赖的、以脂质过氧化为核心驱动力的调节性细胞死亡方式,在形态学、调控机制、生化和遗传学上均区别于凋亡、坏死和焦亡等。近十年研究表明,铁死亡作为细胞内铁代谢、氨基酸代谢、脂质代谢和糖代谢的关键枢纽,广泛参与到神经退行性疾病(阿尔茨海默病、帕金森病和肌萎缩侧索硬化症等)及多器官损伤(缺血再灌注损伤、肝损伤、肾损伤、心脏损伤)等临床病理进程中。本文系统梳理铁死亡的核心调控网络-铁代谢紊乱、抗氧化防御体系失衡及脂质过氧化级联反应,并聚焦于其在中枢神经系统和多个外周器官损伤中的病理意义。在此基础上,系统梳理铁死亡诱导剂和抑制剂在临床研发中的现状,进而分析靶向铁死亡干预相关疾病所面临的细胞类型特异性、组织特异性以及药物稳定性与安全性等方面的挑战,并进一步展望基因治疗技术及精准药物递送系统在铁死亡相关疾病治疗中的应用前景。

关键词: 铁死亡, 神经退行性疾病, 多器官损伤, 靶向干预

Abstract: Ferroptosis is an iron-dependent, regulatory form of cell death driven primarily by lipid peroxidation, and it is distinct from apoptosis, necrosis, and pyroptosis in terms of morphology, regulatory mechanisms, biochemistry, and genetics. Over the past decade, studies have shown that ferroptosis, as a key hub linking intracellular iron metabolism, amino acid metabolism, lipid metabolism, and glucose metabolism, is widely involved in the clinical and pathological processes of neurodegenerative diseases(such as Alzheimers disease, Parkinsons disease, and amyotrophic lateral sclerosis)and multi-organ injury(ischemia-reperfusion injury, liver injury, kidney injury, and cardiac injury). This article systematically reviews the core regulatory network of ferroptosis-iron metabolism disorders, imbalance of the antioxidant defense system, and the lipid peroxidation cascade-and focuses on its pathological significance in the central nervous system and multiple peripheral organ injuries. On this basis, it systematically reviews the current status of ferroptosis inducers and inhibitors in clinical development, and further analyzes the challenges faced in targeting ferroptosis for intervention in related diseases, including cell-type specificity, tissue specificity, and drug stability and safety. It also further discusses the application prospects of gene therapy technologies and precise drug delivery systems in the treatment of ferroptosis-related diseases.

Key words: Ferroptosis, Neurodegenerative diseases, Multiple organ injury, Targeted intervention

中图分类号:

R322.8

梁春惠,初波. 铁死亡调控神经退行性疾病及多器官损伤的机制与靶向干预研究进展[J]. 山东大学学报 (医学版), 2026, 64(10): 71-78.

LIANG Chunhui, CHU Bo. Research progress on the mechanisms and targeted interventions of ferroptosis in regulating neurodegenerative diseases and multiple organ injury[J]. Journal of Shandong University (Health Sciences), 2026, 64(10): 71-78.

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