Since the 1980s, it has been known that the administration of ganglioside GM1 to cultured cells induced or enhanced neuronal differentiation. GM1 mechanism of action relies on its direct interaction and subsequent activation of the membrane tyrosine kinase receptor, TrkA, which naturally serves as NGF receptor. This process is mediated by the sole oligosaccharide portion of GM1, the pentasaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc. Here we detailed the minimum structural requirements of the oligosaccharide portion of GM1 for mediating the TrkA dependent neuritogenic processing. By in vitro and in silico biochemical approaches, we demonstrated that the minimal portion of GM1 required for the TrkA activation is the inner core of the ganglioside’s oligosaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal. The addition of a sialic acid residue at position 3 of the outer galactose of the GM1 oligosaccharide, which forms the oligosaccharide of GD1a, prevented the interaction with TrkA and the resulting neuritogenesis. On the contrary, the addition of a fucose residue at position 2 of the outer galactose, forming the Fucosyl-GM1 oligosaccharide, did not prevent the TrkA-mediated neuritogenesis.

自 20 世纪 80 年代以来，人们已经知道向培养细胞施用神经节苷脂 GM1 可诱导或增强神经元分化。 GM1 的作用机制依赖于其直接相互作用以及随后激活膜酪氨酸激酶受体 TrkA（天然充当 NGF 受体）。该过程由 GM1 的唯一寡糖部分，即五糖 β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal- 介导。 (1-4)-β-Glc。在这里，我们详细介绍了 GM1 寡糖部分介导 TrkA 依赖性神经突发生过程的最低结构要求。通过体外和计算机生化方法，我们证明 TrkA 激活所需的 GM1 的最小部分是神经节苷脂寡糖 β-Gal-(1-3)-β-GalNAc-(1-4)- 的内核。 [α-Neu5Ac-(2-3)]-β-Gal。在 GM1 寡糖（形成 GD1a 寡糖）的外部半乳糖的第 3 位添加唾液酸残基，阻止了与 TrkA 的相互作用以及由此产生的神经突发生。相反，在外部半乳糖的2位添加岩藻糖残基，形成岩藻糖基-GM1寡糖，并不能阻止TrkA介导的神经突发生。