The current aging of the world population will increase the number of people suffering from brain degenerative diseases such as Alzheimer's disease (AD). There are evidence showing that the use of growth factors such as BMP-9 could restored cognitive function as it acts on many AD hallmarks at the same time. However, BMP-9 is a big protein expensive to produce that can hardly access the central nervous system. We have therefore developed a small peptide, SpBMP-9, derived from the knuckle epitope of BMP-9 and showed its therapeutic potential in a previous study. Since it is known that the native protein, BMP-9, can act in synergy with other growth factors in the context of AD, here we study the potential synergistic effect of various combinations of SpBMP-9 with bFGF, EGF, IGF-2 or NGF on the cholinergic differentiation of human neuroblastoma cells SH-SY5Y. We found that, in opposition to IGF-2 or EGF, the combination of SpBMP-9 with bFGF or NGF can stimulate to a greater extent the neurite outgrowth and neuronal differentiation toward the cholinergic phenotype as shown by expression and localization of the neuronal markers NSE and VAchT and the staining of intracellular calcium. Those results strongly suggest that SpBMP-9 plus NGF or bFGF are promising therapeutic combinations against AD that required further attention.

当前世界人口的老龄化将增加罹患脑退化性疾病（例如阿尔茨海默氏病（AD））的人数。有证据表明，使用生长因子如BMP-9可以恢复认知功能，因为它同时作用于许多AD标志。但是，BMP-9是一种昂贵的生产大蛋白，几乎无法进入中枢神经系统。因此，我们开发了一种小肽SpBMP-9，该肽衍生自BMP-9的指节抗原决定簇，并在先前的研究中显示了其治疗潜力。由于已知在AD的情况下，天然蛋白BMP-9可以与其他生长因子协同作用，因此在此我们研究SpBMP-9与bFGF，EGF，IGF-2或NGF对人神经母细胞瘤细胞SH-SY5Y的胆碱能分化。我们发现，与IGF-2或EGF相反，SpBMP-9与bFGF或NGF的结合可在更大程度上刺激神经突生长和神经元向胆碱能表型的分化，如神经元标记NSE的表达和定位所示。和VAchT以及细胞内钙的染色。这些结果强烈表明，SpBMP-9加NGF或bFGF是抗AD的有希望的治疗组合，需要进一步关注。SpBMP-9与bFGF或NGF的组合可在更大程度上刺激神经突生长和神经元向胆碱能表型的分化，这由神经元标记NSE和VAchT的表达和定位以及细胞内钙的染色显示。这些结果强烈表明，SpBMP-9加NGF或bFGF是抗AD的有希望的治疗组合，需要进一步关注。SpBMP-9与bFGF或NGF的组合可在更大程度上刺激神经突生长和神经元向胆碱能表型的分化，这由神经元标记NSE和VAchT的表达和定位以及细胞内钙的染色显示。这些结果强烈表明，SpBMP-9加NGF或bFGF是抗AD的有希望的治疗组合，需要进一步关注。