半乳糖凝集素-1,一种β-半乳糖苷结合蛋白,在各种组织中广泛表达并表现出多种生物活性。我们之前获得了以下发现:1)薯白皂苷元,类固醇皂苷元,在阿尔茨海默病(AD)模型中促进大脑轴突再生并恢复记忆缺陷,5XFAD小鼠;2)海马中Galectin-1蛋白的神经元特异性过表达恢复了记忆障碍,并促进了5XFAD小鼠脑中的轴突再生;3)Secernin-1,表达Galectin-1的轴突的对应物和轴突指导分子,由前额叶皮层神经元分泌,以促进从海马到前额叶皮层的轴突引导。然而,它从未阐明,皂苷元信号增加半乳糖凝集素-1和Secernin-1或不。这里,我们发现,在原代培养的神经元和5XFAD小鼠脑中,皂苷元处理上调海马中Galectin-1的蛋白水平.此外,通过处理1,25D3-膜相关的快速反应类固醇结合受体(1,25D3-MARRS)的中和抗体,减少了皂苷元诱导的半乳糖凝集素-1的上调,皂苷元的直接结合受体。重要的是,海马神经元中半乳糖凝集素-1的敲减抑制了皂苷元的轴突生长活性。此外,通过向5XFAD小鼠施用皂苷元,在前额叶皮层神经元中Secernin-1的表达水平也增加。这些发现表明薯不上皂苷元是促进AD脑中半乳糖凝集素-1-Secernin-1介导的轴突生长的合适化合物。
Galectin-1, a β-galactosides-binding protein, is widely expressed in various tissues and exhibits diverse biological activities. We previously obtained following findings; 1) Diosgenin, a steroid sapogenin, promoted axonal regeneration in the brain and recovered memory deficits in a model of Alzheimer\'s disease (AD), 5XFAD mouse; 2) Neuron-specific overexpression of Galectin-1 protein in the hippocampus recovered memory impairment and promoted axonal regeneration in the brain in 5XFAD mice; 3) Secernin-1, a counterpart and axonal guidance molecule for Galectin-1-expressing axons, was secreted from the prefrontal cortical neurons to promote axonal guidance from the hippocampus to the prefrontal cortex. However, it has never been elucidated that diosgenin signaling increase Galectin-1 and Secernin-1 or not. Here, we found that diosgenin treatment upregulated the protein level of Galectin-1 in the hippocampus both in primary cultured neurons and in 5XFAD mouse brains. In addition, diosgenin-induced upregulation of Galectin-1 was diminished by treatment of a neutralizing antibody of 1,25D3-membrane-associated rapid response steroid-binding receptor (1,25D3-MARRS), a direct binding receptor for diosgenin. Importantly, knockdown of Galectin-1 in hippocampal neurons inhibited axonal growth activity of diosgenin. Furthermore, the expression level of Secernin-1 was also increased in prefrontal cortical neurons by administration of diosgenin to 5XFAD mice. These findings suggest that diosgenin is a suitable compound to facilitate Galectin-1-Secernin-1-mediated axonal growth in AD brains.