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半乳糖凝集素:新型抗炎药物靶点。

Galectins: novel anti-inflammatory drug targets.

作者信息

Liu Fu-Tong

机构信息

Department of Dermatology, University of California-Davis, School of Medicine, Sacramento.

出版信息

Expert Opin Ther Targets. 2002 Aug;6(4):461-8. doi: 10.1517/14728222.6.4.461.

Abstract

Galectins are a protein family defined by their affinity for beta-galactosides and consensus sequences. They are pleiotropic regulators involved in a multitude of functions, both in and out of the cell. Extracellularly, they have the potential to bind to various surface receptors on a variety of cell types as well as extracellular matrix (ECM) proteins, thus causing cell activation or apoptosis, modulating cell adhesion and inducing cell migration. Intracellularly, they can regulate cell growth, apoptosis and cell cycle progression. Galectins are either pro-inflammatory or anti-inflammatory. Some, such as galectin-1, may be employed as anti-inflammatory agents, while others, such as galectin-3, are evidently suitable targets for anti-inflammatory drugs. The extracellular functions of galectins involve their lectin-carbohydrate interactions and thus their carbohydrate ligands or mimetics would be suitable inhibitors. While the intracellular functions of galectins do not appear to engage lectin-carbohydrate interactions, the carbohydrate-binding sites of these proteins may still be involved. Therefore, the same inhibitors may be used regardless of whether intracellular or extracellular galectins are to be targeted.

摘要

半乳糖凝集素是一类因其对β-半乳糖苷的亲和力和共有序列而定义的蛋白质家族。它们是多效性调节剂,参与细胞内外的多种功能。在细胞外,它们有可能与多种细胞类型上的各种表面受体以及细胞外基质(ECM)蛋白结合,从而导致细胞激活或凋亡,调节细胞黏附并诱导细胞迁移。在细胞内,它们可以调节细胞生长、凋亡和细胞周期进程。半乳糖凝集素要么具有促炎作用,要么具有抗炎作用。一些,如半乳糖凝集素-1,可作为抗炎剂,而其他一些,如半乳糖凝集素-3,则显然是抗炎药物的合适靶点。半乳糖凝集素的细胞外功能涉及其凝集素-碳水化合物相互作用,因此它们的碳水化合物配体或模拟物将是合适的抑制剂。虽然半乳糖凝集素的细胞内功能似乎不涉及凝集素-碳水化合物相互作用,但这些蛋白质的碳水化合物结合位点可能仍然参与其中。因此,无论靶向细胞内还是细胞外的半乳糖凝集素,都可以使用相同的抑制剂。

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