Khan Muhammad S, Hu Qichan, Okeibunor Kendrix, Ma Liang, Bopassa Jean C
Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Front Physiol. 2025 Aug 28;16:1641323. doi: 10.3389/fphys.2025.1641323. eCollection 2025.
Ferroptosis is an iron-dependent programmed cell death that plays an important role in neurodegenerative and neuropsychiatric diseases. In the present study, we have highlighted how different risk factors are involved in the induction of ferroptosis in brain cells. In addition, we also demonstrated how ferroptosis plays an important role in different brain diseases. In our study why we focused and elaborated on the mechanisms of ferroptosis only in brain cells (Neurons, oligodendrocytes, and microglia) because they are particularly vulnerable to such kind of cell death. Additionally, brain cells are more dependent on mitochondrial function, iron regulation, and high levels of polyunsaturated fatty acids (PUFAs) as compared to peripheral body cells. Highlighting ferroptosis is more important because it has demonstrated several important mechanisms of neuronal injury and dysfunction which provides a deep understanding of the etiology of various brain diseases that were not sufficiently described by other programmed cell death pathways. Therefore, it has led to the exploration of new therapeutic strategies against various brain diseases and thus targeting ferroptosis-related proteins opens a new therapeutic window for several incurable brain diseases, and various ferroptosis regulators are now under clinical trials. However, their validation as a preclinical therapeutic agent is needed. Interestingly, here in our study we also summarize the most recent potential therapeutic targets and promising interventions which will provide a beam of light for future therapies against major brain diseases.
铁死亡是一种铁依赖性程序性细胞死亡,在神经退行性疾病和神经精神疾病中起重要作用。在本研究中,我们强调了不同风险因素如何参与脑细胞中铁死亡的诱导。此外,我们还证明了铁死亡在不同脑部疾病中如何发挥重要作用。在我们的研究中,我们之所以专注并详细阐述仅在脑细胞(神经元、少突胶质细胞和小胶质细胞)中的铁死亡机制,是因为它们特别容易受到这种细胞死亡的影响。此外,与外周体细胞相比,脑细胞更依赖线粒体功能、铁调节和高水平的多不饱和脂肪酸(PUFA)。强调铁死亡更为重要,因为它已证明了几种重要的神经元损伤和功能障碍机制,这为各种脑部疾病的病因提供了深入理解,而其他程序性细胞死亡途径对此描述不足。因此,它促使人们探索针对各种脑部疾病的新治疗策略,因此靶向铁死亡相关蛋白为几种无法治愈的脑部疾病打开了新的治疗窗口,并且各种铁死亡调节剂目前正在进行临床试验。然而,需要将它们验证为临床前治疗剂。有趣的是,在我们的研究中,我们还总结了最新的潜在治疗靶点和有前景的干预措施,这将为未来针对主要脑部疾病的治疗提供一线希望。