Metabolic Reprogramming in Sickle Cell Diseases: Pathophysiology and Drug Discovery Opportunities.
Metabolic Reprogramming in Sickle Cell Diseases: Pathophysiology and Drug Discovery Opportunities.
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DOI：
10.3390/ijms23137448
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发表时间：
2022-07-04
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
镰状细胞病（SCD）是一种影响全世界数百万人的遗传性疾病。慢性贫血、溶血和血管病变与SCD有关，它们的作用已被很好地描述。这些症状源于血红蛋白（Hb）聚合，这是SCD分子发病机制中的主要事件，并导致红细胞或红细胞（RBC）镰状坏死、僵硬和血管闭塞。这种疾病是由β-珠蛋白基因第6位突变引起的，该基因编码镰状血红蛋白（HbS）而不是正常成人血红蛋白（HbA），在缺氧条件下聚合成刚性纤维，扭曲红细胞的形状。只有少数治疗方法可用，最近批准的治疗方法的普遍有效性仍在监测中。在这篇综述中，我们首先关注镰状红细胞如何改变代谢，然后强调这种理解如何揭示涉及疾病发病机制的潜在靶点，这可以用来创造新的治疗方法。
Sickle cell disease (SCD) is a genetic disorder that affects millions of individuals worldwide. Chronic anemia, hemolysis, and vasculopathy are associated with SCD, and their role has been well characterized. These symptoms stem from hemoglobin (Hb) polymerization, which is the primary event in the molecular pathogenesis of SCD and contributes to erythrocyte or red blood cell (RBC) sickling, stiffness, and vaso-occlusion. The disease is caused by a mutation at the sixth position of the β-globin gene, coding for sickle Hb (HbS) instead of normal adult Hb (HbA), which under hypoxic conditions polymerizes into rigid fibers to distort the shapes of the RBCs. Only a few therapies are available, with the universal effectiveness of recently approved therapies still being monitored. In this review, we first focus on how sickle RBCs have altered metabolism and then highlight how this understanding reveals potential targets involved in the pathogenesis of the disease, which can be leveraged to create novel therapeutics for SCD.
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