Fig. 4

Design and structures of CNTF small-molecule mimetics and their mechanism of action to enhance formation of NPCs and mature neurons. a Protein Data Base rendering of one 4-helix bundle of truncated human CNTF (Residues 2–187), generated from CNTF. Only one protein chain is shown for clarity. Residues 149GGLFEKKL156 are shown as a tube model, while the rest of the sequence are presented as ribbon [98]. The structures of P6 and P021 are also shown. From the neurogenic 11-mer, Ac-VGDGGLFEKKL-NH₂ (P6), a truncated, still neurogenic pentamer, with an adamantylated glycine group (red oval), Ac-DGGLA^G-NH₂ (P021) was designed [191]. b P6 and P021 enhance neural progenitor cells (NPCs) formation and maturation and integration of new-born neurons by competitively inhibiting the LIF signaling and increasing BDNF expression respectively [99, 180, 181, 191, 192]