Purnell Marcy C
School of Leadership and Advanced Nursing Practice, The University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Discov Med. 2019 Nov-Dec;28(155):219-227.
Sickle cell disease (SCD), the most common severe monogenic disease in the world, is known for the hallmark vaso-occlusive crises that cause great suffering and degradation of health for these patients. In 1949, the discovery of the abnormal sickle cell hemoglobin protein (HbS) β-globin chain revealed a mutation where glutamic acid is replaced with a valine (β6Glu→Val). From this discovery came the pathophysiological mechanism based on the abnormal polymerization of deoxy-HbS. While an important discovery, this initial mechanism has yet been able to account for the cascade of events that trigger these crises and has therefore offered few treatment options for these patients. In red blood cells, alterations to membrane structure lead to changes in their biomechanical behaviors. A literature review has been conducted and a possible sickle cell pathophysiological mechanism that involves the potential for abnormal polymerization of the critical actin protein (in the spectrin-actin complex) within the red blood cell cytoskeleton has been identified. This review will discuss the interaction of valine and glucose on the HbS molecule and how it may lead to a destabilization of the HbS red blood cell cytoskeleton and SCD crises.
镰状细胞病（SCD）是世界上最常见的严重单基因疾病，以标志性的血管阻塞性危象而闻名，这些危象给患者带来巨大痛苦并损害其健康。1949年，异常的镰状细胞血红蛋白蛋白（HbS）β珠蛋白链的发现揭示了一种突变，即谷氨酸被缬氨酸取代（β6Glu→Val）。基于此发现，产生了基于脱氧HbS异常聚合的病理生理机制。虽然这是一项重要发现，但这一初始机制尚无法解释引发这些危象的一系列事件，因此为这些患者提供的治疗选择很少。在红细胞中，膜结构的改变会导致其生物力学行为发生变化。我们进行了文献综述，并确定了一种可能的镰状细胞病理生理机制，该机制涉及红细胞细胞骨架内关键肌动蛋白（在血影蛋白-肌动蛋白复合物中）异常聚合的可能性。本综述将讨论缬氨酸和葡萄糖在HbS分子上的相互作用，以及它如何导致HbS红细胞细胞骨架的不稳定和SCD危象。
