Sousa Ricardo A L, Yehia Asmaa, Abulseoud Osama A
Department of Psychiatry and Psychology, Mayo Clinic Arizona, Phoenix, AZ, United States.
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Front Neurosci. 2023 Jul 24;17:1237153. doi: 10.3389/fnins.2023.1237153. eCollection 2023.
Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), is associated with the persistence of pre-existing or the emergence of new neurological and psychiatric manifestations as a part of a multi-system affection known collectively as "post-COVID syndrome." Cognitive decline is the most prominent feature among these manifestations. The underlying neurobiological mechanisms remain under intense investigation. Ferroptosis is a form of cell death that results from the excessive accumulation of intracellular reactive iron, which mediates lipid peroxidation. The accumulation of lipid-based reactive oxygen species (ROS) and the impairment of glutathione peroxidase 4 (GPX4) activity trigger ferroptosis. The COVID-19-associated cytokine storm enhances the levels of circulating pro-inflammatory cytokines and causes immune-cell hyper-activation that is tightly linked to iron dysregulation. Severe COVID-19 presents with iron overload as one of the main features of its pathogenesis. Iron overload promotes a state of inflammation and immune dysfunction. This is well demonstrated by the strong association between COVID-19 severity and high levels of ferritin, which is a well-known inflammatory and iron overload biomarker. The dysregulation of iron, the high levels of lipid peroxidation biomarkers, and the inactivation of GPX4 in COVID-19 patients make a strong case for ferroptosis as a potential mechanism behind post-COVID neuropsychiatric deficits. Therefore, here we review the characteristics of iron and the attenuation of ferroptosis as a potential therapeutic target for neuropsychiatric post-COVID syndrome.
新型冠状病毒肺炎（COVID-19）由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起，与先前存在的或新出现的神经和精神症状的持续存在有关，这些症状是多系统受累的一部分，统称为“新冠后综合征”。认知衰退是这些症状中最突出的特征。其潜在的神经生物学机制仍在深入研究中。铁死亡是一种细胞死亡形式，由细胞内活性铁的过度积累导致，活性铁介导脂质过氧化。基于脂质的活性氧（ROS）积累和谷胱甘肽过氧化物酶4（GPX4）活性受损会引发铁死亡。与COVID-19相关的细胞因子风暴会提高循环促炎细胞因子水平，并导致免疫细胞过度激活，这与铁代谢失调密切相关。重症COVID-19的主要发病机制之一是铁过载。铁过载会促进炎症状态和免疫功能障碍。COVID-19严重程度与高水平铁蛋白之间的强关联很好地证明了这一点，铁蛋白是一种众所周知的炎症和铁过载生物标志物。COVID-19患者的铁代谢失调、脂质过氧化生物标志物的高水平以及GPX4的失活有力地证明了铁死亡是新冠后神经精神缺陷背后的潜在机制。因此，我们在此综述铁的特征以及作为新冠后神经精神综合征潜在治疗靶点的铁死亡的减轻。
