ICMR-National Institute of Research in Tribal Health, India.
ICMR-National Institute of Research in Tribal Health, India.
Gene. 2024 Nov 30;928:148805. doi: 10.1016/j.gene.2024.148805. Epub 2024 Jul 28.
Sickle cell disease is a catastrophic inflammatory disorder characterized by microvascular vaso-occlusion, leading to high morbidity and increased mortality. P-selectin, a cell adhesion molecule, plays a crucial role in the pathogenesis and severity of sickle cell disease. Its expression and binding with its ligand PSGL-1 is involved in various mechanisms that contribute to inflammation and immune response, resulting in complications in sickle cell disease. Preclinical data have verified the efficacy of P-Selectin inhibition in mitigating vaso-occlusive events and severity of disease. Currently clinical trials are ongoing to evaluate the safety and efficiency of P-Selectin-targeted therapies and concede the challenges and limitations associated with their use. Despite of its proven role in reducing severity in sickle cell disease, future research should focus on identifying other novel targets within the adhesion cascade and explore combination therapies. Conducting trials and addressing concerns about accessibility are crucial steps towards fully harnessing the potential of P selectin inhibitors as a groundbreaking treatment option. This review focuses on understanding the role of p selectin and its interactions with molecules involved in inflammation providing insights about the molecular etiology, pathophysiology, and potential therapeutic targets in sickle cell disease.
镰状细胞病是一种灾难性的炎症性疾病，其特征是微血管血管阻塞，导致高发病率和死亡率增加。P 选择素是一种细胞黏附分子，在镰状细胞病的发病机制和严重程度中起着关键作用。其表达及其与配体 PSGL-1 的结合涉及多种导致炎症和免疫反应的机制，从而导致镰状细胞病的并发症。临床前数据已经证实了 P 选择素抑制在减轻血管阻塞事件和疾病严重程度方面的疗效。目前正在进行临床试验，以评估 P 选择素靶向治疗的安全性和有效性，并承认与使用相关的挑战和限制。尽管 P 选择素已被证明可降低镰状细胞病的严重程度，但未来的研究应侧重于确定黏附级联反应中的其他新靶标，并探索联合治疗方法。开展试验和解决可及性问题是充分利用 P 选择素抑制剂作为突破性治疗选择的关键步骤。本综述重点探讨了 p 选择素的作用及其与炎症相关分子的相互作用，为镰状细胞病的分子病因、病理生理学和潜在治疗靶点提供了深入了解。
