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CD47 在大脑与神经退行性变中的作用:神经炎症途径相关研究进展

CD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways.

机构信息

Department of Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916188635, Iran.

Department of Physiology, School of Medicine, Universidad Antonio Nariño, Bogotá 111511, Colombia.

出版信息

Molecules. 2021 Jun 28;26(13):3943. doi: 10.3390/molecules26133943.

Abstract

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.

摘要

CD47 是一种属于免疫球蛋白 (Ig) 超家族的受体,广泛表达于细胞膜上。通过与 SIRPα、TSP-1、整合素和 SH2 结构域结合蛋白酪氨酸磷酸酶底物-1(SHPS-1)等配体相互作用,CD47 调节细胞黏附、增殖、凋亡、迁移、稳态和免疫系统等多种功能。在这方面,先前的研究表明 CD47 通过巨噬细胞调节吞噬作用、中性粒细胞的迁移以及 T 细胞、树突状细胞和 B 细胞的激活。此外,有几项研究报道了 CD47 受体在多种疾病中的表达增加,包括急性淋巴细胞白血病 (ALL)、慢性髓系白血病、非霍奇金淋巴瘤 (NHL)、多发性骨髓瘤 (MM)、膀胱癌、急性髓系白血病 (AML)、戈谢病、多发性硬化症和中风等。通过不同的方法学已经确定了 CD47 细胞受体在中枢神经系统大多数固有细胞上的普遍表达。然而,关于其在中枢神经系统中不同神经退行性病变发展中的精确功能的信息很少。因此,在将 CD47 和 SIRP 作为针对影响人类的各种神经退行性疾病的可药物靶标进行开发之前,需要进一步研究 CD47 和 SIRP 的特定功能和作用。本综述试图总结 CD47 和 SIRP 的作用及其在神经退行性疾病中的治疗潜力。

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