Department of Psychology, Division of Neuroscience, Sapienza University of Rome, 00185 Rome, Italy.
Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Biomolecules. 2020 Nov 13;10(11):1551. doi: 10.3390/biom10111551.
Ferroptosis is an iron-dependent form of regulated cell death, arising from the accumulation of lipid-based reactive oxygen species when glutathione-dependent repair systems are compromised. Lipid peroxidation, mitochondrial impairment and iron dyshomeostasis are the hallmark of ferroptosis, which is emerging as a crucial player in neurodegeneration. This review provides an analysis of the most recent advances in ferroptosis, with a special focus on Friedreich's Ataxia (FA), the most common autosomal recessive neurodegenerative disease, caused by reduced levels of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and antioxidant defenses. The hypothesis is that the iron-induced oxidative damage accumulates over time in FA, lowering the ferroptosis threshold and leading to neuronal cell death and, at last, to cardiac failure. The use of anti-ferroptosis drugs combined with treatments able to activate the antioxidant response will be of paramount importance in FA therapy, such as in many other neurodegenerative diseases triggered by oxidative stress.
铁死亡是一种依赖于铁的细胞程序性死亡形式，是由于谷胱甘肽依赖的修复系统受损时脂质活性氧的积累引起的。脂质过氧化、线粒体损伤和铁代谢失衡是铁死亡的特征，铁死亡正在成为神经退行性变的关键参与者。本文对铁死亡的最新进展进行了分析，特别关注弗里德里希共济失调症（FA），这是最常见的常染色体隐性神经退行性疾病，由线粒体蛋白 frataxin 水平降低引起，frataxin 参与铁-硫簇合成和抗氧化防御。该假说认为，FA 中随着时间的推移，铁诱导的氧化损伤不断积累，降低铁死亡的阈值，导致神经元细胞死亡，最终导致心力衰竭。在 FA 治疗中，使用抗铁死亡药物结合能够激活抗氧化反应的治疗方法将是至关重要的，这在许多其他由氧化应激引发的神经退行性疾病中也是如此。
