Ferroptosis in health and disease
Ferroptosis in health and disease
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DOI：
10.1016/j.redox.2024.103211
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发表时间：
2024-06-21
期刊：
影响因子：
11.4
通讯作者：
Conrad，Marcus
中科院分区：
文献类型：
--
作者：
Berndt，Carsten;Alborzinia，Hamed;Conrad，Marcus
铁下垂是一种普遍存在的非凋亡形式的细胞死亡，与各种退行性疾病和恶性肿瘤高度相关。铁下垂的标志是膜磷脂中含有的多不饱和脂肪酸不受控制和压倒性的过氧化，最终导致质膜破裂。铁死亡的独特之处在于，它本质上是一种自发的、非催化的化学过程，基于受干扰的铁和氧化还原稳态，导致细胞死亡过程，但它仍然受到许多代谢节点的调节，这些代谢节点影响细胞对铁死亡的易感性。在影响铁下垂敏感性的各种淋巴结中，有几个已经成为药物干预的有希望的候选者，使铁下垂相关蛋白成为治疗许多目前无法治愈的疾病的有吸引力的靶点。在此，德国范围内专注于铁下垂研究的研究联盟的现任成员，以及对这一快速发展和令人兴奋的研究领域做出开创性贡献的铁下垂关键外部专家，聚集在一起，提供了一份全面的，最先进的关于铁下垂的综述。具体主题包括：基本机制，体内相关性，专门的方法，化学和药理学工具，以及铁下垂对疾病病因病理学和进展的潜在贡献。我们希望这篇文章不仅将为该领域的知名科学家和新手提供关于铁下垂的多个方面的概述，而且还将鼓励进一步研究调节铁下垂的分子途径，最终目标是开发新的药物治疗方法来解决与铁下垂相关或由铁下垂引起的各种疾病。
Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells’ susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with – or caused by – ferroptosis.