A small peptide derived from BMP-9 can increase the effect of bFGF and NGF on SH-SY5Y cells differentiation.

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.