Nio-Kobayashi Junko, Itabashi Tetsuya
Laboratory of Histology and Cytology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Front Neuroanat. 2021 Oct 15;15:767330. doi: 10.3389/fnana.2021.767330. eCollection 2021.
Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and-9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,-3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. -glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6--acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.
半乳糖凝集素是β-半乳糖苷结合凝集素，在哺乳动物中由15个成员组成。半乳糖凝集素-1、-3、-4、-8和-9主要在中枢神经系统（CNS）中表达，并调节各种生理和病理过程。本综述总结了目前关于半乳糖凝集素在中枢神经系统中的细胞表达和作用的知识，并讨论了它们在神经突生长、髓鞘形成和神经干/祖细胞龛中的功能，以及在缺血/缺氧/创伤性损伤和神经退行性疾病（如多发性硬化症）中的功能。半乳糖凝集素在神经元和胶质细胞中均有表达。半乳糖凝集素-1主要在运动神经元中表达，而半乳糖凝集素-3阳性神经元广泛分布于整个大脑，尤其是在下丘脑，表明其在调节体内平衡、应激反应和内分泌/自主神经系统中的作用。星形胶质细胞主要含有半乳糖凝集素-1，随着其激活，半乳糖凝集素-3和-9会上调。活化而非静止的小胶质细胞含有半乳糖凝集素-3，支持其吞噬活性。半乳糖凝集素-1、-3和-4在少突胶质细胞分化过程中特异性表达。小胶质细胞中的半乳糖凝集素-3促进少突胶质细胞分化和髓鞘形成，而半乳糖凝集素-1和轴突半乳糖凝集素-4抑制其分化和髓鞘形成。半乳糖凝集素-1和-3阳性细胞参与脑室下区和海马齿状回神经干细胞龛的形成，以及新生神经元和胶质细胞向嗅球或受损病变的迁移。在神经退行性疾病中，半乳糖凝集素-1、-8和-9具有神经保护和抗炎活性。半乳糖凝集素-3促进促炎作用；然而，它在恢复期也起着重要作用。到目前为止，已经鉴定出几种配体糖缀合物，如层粘连蛋白、整合素、神经细胞粘附分子L1、硫脂、神经纤毛蛋白-1/丛状蛋白A4受体复合物、髓样细胞触发受体2以及T细胞免疫球蛋白和粘蛋白结构域。由β1,6-N-乙酰葡糖胺基转移酶V（Mgat5/GnTV）介导的淋巴细胞和少突胶质前体细胞上的聚糖分支影响半乳糖凝集素结合，调节神经退行性疾病中的炎症反应和髓鞘再生。脱硫酸化的糖胺聚糖如硫酸角质素是半乳糖凝集素的潜在配体，尤其是半乳糖凝集素-3，可调节神经再生。半乳糖凝集素根据细胞类型、环境以及翻译后修饰（包括氧化、磷酸化、S-亚硝基化和切割）具有多种功能，但半乳糖凝集素及其配体糖缀合物的表达模式应该有一定规律，可能与细胞中的葡萄糖代谢有关。
