Russo Annamaria, Patanè Giuseppe Tancredi, Calderaro Antonella, Barreca Davide, Tellone Ester, Putaggio Stefano
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres 31, 98166 Messina, Italy.
Int J Mol Sci. 2025 Apr 13;26(8):3675. doi: 10.3390/ijms26083675.
Sickle cell disease (SCD) is an inherited hemoglobin disorder that is widespread across the globe. It is characterized by a very complex pathogenesis, but at the basis of the disease is the mutation of the HBB gene, which determines the production of a mutated hemoglobin: sickle cell hemoglobin (HbS). The polymerization of HbS, which occurs when the protein is in a deoxygenated state, and the greater fragility of sickle cell red blood cells (sRBCs) determine the release of iron, free heme, and HbS in the blood, favoring oxidative stress and the production of reactive oxygen species (ROS). These features are common to the features of a new model of cell death known as ferroptosis, which is characterized by the increase of iron and ROS concentrations and by the inhibition of glutathione peroxidase 4 (GPx4) and the System Xc. In this context, this review aims to discuss the potential molecular and biochemical pathways of ferroptosis involved in SCD, aiming to highlight possible tags involved in treating the disease and inhibiting ferroptosis.
镰状细胞病（SCD）是一种遗传性血红蛋白疾病，在全球广泛存在。其发病机制非常复杂，但其根本原因是HBB基因突变，该突变决定了一种突变血红蛋白的产生：镰状细胞血红蛋白（HbS）。当蛋白质处于脱氧状态时，HbS会发生聚合，同时镰状红细胞（sRBCs）的更大脆性决定了血液中铁、游离血红素和HbS的释放，这有利于氧化应激和活性氧（ROS）的产生。这些特征与一种称为铁死亡的新型细胞死亡模型的特征相同，铁死亡的特征是铁和ROS浓度增加，以及谷胱甘肽过氧化物酶4（GPx4）和Xc系统的抑制。在此背景下，本综述旨在讨论SCD中涉及的铁死亡潜在分子和生化途径，旨在突出可能用于治疗该疾病和抑制铁死亡的靶点。
Zotero 插件