Activation of Trk receptors and their main post-receptor signaling pathways by dipeptide mimetics of NGF, BDNF, and NT-3
| Parent neurotrophin | Code | Neurotrophin loop | Concentration (M) | Trk receptor activation | Activation of post-receptor signaling cascades | ||
|---|---|---|---|---|---|---|---|
| PI3K/Akt | MAPK/ERK | PLC-γ1 | |||||
| NGF | GK-2 [37, 41] | 4 | 10–8 | TrkA | ++ | ns | ++ |
| GK-6 [37, 41] | 1 | 10–6 | TrkA | + | + | + | |
| GTS-115 [34, 41] | 3 | 10–6 | TrkA | ++ | + | + | |
| BDNF | GSB-106 [38, 41] | 4 | 10–8 | TrkB | + | ++ | ++ |
| GSB-214 [38, 41] | 1 | 10–7 | TrkB | + | ns | ++ | |
| GTS-201 [35, 41] | 2 | 10–7 | TrkB | ns | + | ++ | |
| NT-3 | GTS-301 [33, 42] | 4 | 10–6 | TrkC | ns | ++ | ++ |
| GTS-302 [36, 42] | 10–6 | TrkC | ++ | ++ | + | ||
Full-length NGF, BDNF and NT-3 at concentrations of 10–9 M were used as positive controls. Trk: tyrosine kinase; NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; NT-3: neurotrophin-3; MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinase; PLC-γ1: phospholipase C-gamma; GK-2: bis-(monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide; GK-6: bis-(N-aminocaproyl-glycyl-L-lysine) hexamethylenediamide; GSB-106: bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide; GSB-214: bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide; GTS-115: bis-(N-gamma-oxybutyryl-L-lysyl-L-histidine) hexamethylenediamide; GTS-201: bis-(N-hexanoyl-L-seryl-L-lysine) hexamethylenediamide; GTS-301: bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) hexamethylenediamide; GTS-302: bis-(N-gamma-oxybutyryl-L-glutamyl-L-asparagine) hexamethylenediamide; +: the effect is inferior to the full-length neurotrophin in terms of intensity and/or duration; ++: the effect is comparable to the full-length neurotrophin in terms of intensity and duration; ns: non-significant