Molecular Mechanisms and Therapeutic Advances in Sickle Cell Disease: Insights into Genetics, Pathophysiology, and Treatment Strategies

Abstract

Red blood cells (RBCs) with aberrant haemoglobin S (HbS) are indicative of sickle cell disease (SCD), a severe hereditary hemoglobinopathy. The characteristics of haemoglobin are changed by a single point mutation in the β-globin gene, which causes a valine to replace glutamic acid at position six. RBCs sickle as a result of HbS molecules polymerising in a deoxygenated environment. Numerous pathophysiological processes, such as haemolysis, vaso-occlusion, inflammation, oxidative stress, endothelial dysfunction, and multi-organ damage, are facilitated by these malformed cells. The molecular causes of sickle cell disease (SCD) are examined in this review, ranging from genetic mutations and aberrant protein interactions to cellular reactions and systemic effects. The dynamics of polymerisation, aberrant red cell ion channels, inflammation, thrombotic consequences, and the function of nitric oxide bioavailability are highlighted. We also discuss current developments in gene-based and pharmacologic therapy, such as gene editing techniques, hydroxyurea, antisickling medicines, and monoclonal antibodies. Translational attempts to create tailored therapies that aim to enhance the disease prognosis and quality of life for patients globally have been spurred by a thorough understanding of SCD at the molecular level.