Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture
Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture
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DOI：
10.1111/jnc.12408
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发表时间：
2014-01-01
影响因子：
4.7
通讯作者：
Kaur, Gurcharan
中科院分区：
文献类型：
--
作者：
Loers, Gabriele;Saini, Vedangana;Kaur, Gurcharan
聚唾液酸（PSA）是发育中的神经系统和成人神经可塑性中细胞间相互作用的主要调节剂。PSA作为一种高水结合能力的多阴离子分子，增加了细胞间隙，为细胞运动创造了有利条件。PSA增强干细胞迁移和轴突路径寻找，促进受损周围和中枢神经系统的修复，从而促进再生。下一步，我们将开发一种改进的基于PSA的方法来治疗神经系统损伤，我们寻找了一种模拟PSA的小有机化合物，并确定了一种模拟PSA的5-壬基羟色胺草酸盐，被描述为一种选择性5-羟色胺受体1B （5-HT1B）激动剂。与PSA类似，5-壬基色胺与PSA特异性单克隆抗体735结合，促进培养的原代神经元的神经突生长和雪旺细胞的形成过程，保护神经元免受氧化应激，减少星形胶质细胞的迁移，并增强体外髓鞘形成。此外，壬基色胺处理增强了神经细胞粘附分子（NCAM）及其多唾液化形式PSA-NCAM的表达，并降低了培养的神经母细胞瘤细胞中微管相关蛋白MAP2的表达。这些结果表明，5-壬基氧基色胺模拟PSA并触发PSA介导的功能，从而有助于促进哺乳动物外周和中枢神经系统急性和慢性损伤的恢复。
Polysialic acid (PSA) is a major regulator of cell-cell interactions in the developing nervous system and in neural plasticity in the adult. As a polyanionic molecule with high water-binding capacity, PSA increases the intercellular space generating permissive conditions for cell motility. PSA enhances stem cell migration and axon path finding and promotes repair in the lesioned peripheral and central nervous systems, thus contributing to regeneration. As a next step in developing an improved PSA-based approach to treat nervous system injuries, we searched for small organic compounds that mimic PSA and identified as a PSA mimetic 5-nonyloxytryptamine oxalate, described as a selective 5-hydroxytryptamine receptor 1B (5-HT1B) agonist. Similar to PSA, 5-nonyloxytryptamine binds to the PSA-specific monoclonal antibody 735, enhances neurite outgrowth of cultured primary neurons and process formation of Schwann cells, protects neurons from oxidative stress, reduces migration of astrocytes and enhances myelination in vitro. Furthermore, nonyloxytryptamine treatment enhances expression of the neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM and reduces expression of the microtubule-associated protein MAP2 in cultured neuroblastoma cells. These results demonstrate that 5-nonyloxytryptamine mimics PSA and triggers PSA-mediated functions, thus contributing to the repertoire of molecules with the potential to improve recovery in acute and chronic injuries of the mammalian peripheral and central nervous systems.