The aromatic amino acid residues of tumor necrosis factor receptor-1-derived peptide are important for promoting differentiation of neural stem cells.

Neural stem cells have the self-renewal capacity and the ability to differentiate into all types of nerve cells. We previously reported that the tumor necrosis factor receptor-1-derived peptide promotes neural differentiation of fetal rat hippocampal neural stem cells. The tumor necrosis factor receptor-1-derived peptide contains six aromatic amino acid residues among its 14 amino acid residues. To clarify the role of these aromatic amino acid residues in the action of tumor necrosis factor receptor-1-derived peptide on neural stem cells, we synthesized mutant peptides, in which aromatic residues were substituted with alanine, and we assessed their effects. Substitution of the tyrosine residue at position 103 (Y(103)) or 106 (Y(106)), the tryptophan residue at position 107 (W(107)), or the phenylalanine residue at position 112 (F(112)) or 115 (F(115)), decreased the ability of the peptide to promote neurite outgrowth of neural stem cells depending on their concentration. These data suggest that although all five aromatic amino acid residues mediate the action of the tumor necrosis factor receptor-1-derived peptide, their order of importance in this activity is F(115) > Y(103) > W(107) > Y(106) and F(112).