铁死亡与重大慢性疾病

铁死亡是近年发现的一种铁依赖的新型细胞死亡方式，其特征是脂质过氧化物和活性氧簇的过量蓄积。大量研究表明，铁死亡不仅在重大慢性疾病的发生发展过程中发挥重要作用，而且在不同的疾病背景下扮演不同角色。目前认为，铁死亡可抑制肿瘤生长并增加多种肿瘤对化疗药物和免疫治疗的敏感性，因此诱导铁死亡的发生拓展了肿瘤治疗思路。然而，在心脑血管疾病和神经退行性疾病中，铁死亡的发生通过引发正常组织器官损伤和功能丧失直接参与疾病的发生、发展及转归，因此针对心脑血管疾病和神经退行性疾病，抑制铁死亡的发生能够有效预防并延缓这些疾病的发生和发展。本文综述了铁死亡在恶性肿瘤、神经退行性疾病和心脑血管疾病三类不同重大慢性疾病中的最新研究进展及其潜在的作用机制，系统讨论了靶向铁死亡在防治重大慢性疾病中的临床应用前景，为重大慢性疾病的防治提供新的依据。

The role of ferroptosis in chronic diseases

Recently, ferroptosis, an iron-dependent novel type of cell death, has been characterized as an excessive accumulation of lipid peroxides and reactive oxygen species. Emerging studies demonstrate that ferroptosis not only plays an important role in the pathogenesis and progression of chronic diseases, but also functions differently in the different disease context. Notably, it is shown that activation of ferroptosis could potently inhibit tumor growth and increase sensitivity to chemotherapy and immunotherapy in various cancer settings. As a result, the development of more efficacious ferroptosis agonists remains the mainstay of ferroptosis-targeting strategy for cancer therapeutics. By contrast, in non-cancerous chronic diseases, including cardiovascular & cerebrovascular diseases and neurodegenerative diseases, ferroptosis functions as a risk factor to promote these diseases progression through triggering or accelerating tissue injury. As a matter of fact, blocking ferroptosis has been demonstrated to effectively prevent ischemia-reperfusion heart disease in preclinical animal models. Therefore, it is a promising field to develope potent ferroptosis inhibitors for preventing and treating cardiovascular & cerebrovascular diseases and neurodegenerative diseases. In this article, we summarize the most recent progress on ferroptosis in chronic diseases, and draw attention to the possible clinical impact of this recently emerged ferroptosis modalities.