LM22B-10 is a TrkB/TrkC neurotrophic factor receptor activator that induces the activation of TrkB, TrkC, AKT, and ERK in vivo and in vitro. The maximum neurotrophic survival activity of LM22B-10 was higher than that of BDNF (53 ± 7.2% higher than BDNF at 0.7 nM) and NT-3 (91 ± 8.6% higher than NT-3 at 0.7 nM), with EC50 values of 200-300 nM. The pattern of Trk and downstream signalling activation induced by LM22B-10 was different from that of BDNF and NT-3. The mean neurite length induced by LM22B-10 (1,000 nM) was significantly larger, up to 40 µm. LM22B-10 (250-2000 nM) binds TrkB-Fc and TrkC-Fc in a dose-dependent manner. LM22B-10 inhibits the binding of BDNF to TrkB-expressing cells and the binding of NT-3 to TrkC-expressing cells. LM22B-10 promotes cell survival and acts preferentially on TrkB and TrkC. LM22B-10, but not BDNF or NT-3, promotes neuronal growth in an inhibitory environment. LM22B-10 also induces TrkB, TrkC, AKT and ERK activation in cultured hippocampal neurons[1].
LM22B-10 动物研究
Animal study
LM22B-10 activated TrkB, TrkC, AKT and ERK in C57BL/6J mice at a dose of 0.5 mg/kg. LM22B-10 increased the phosphorylation of TrkB-Y817 and TrkC-Y820 at a dose of 50 mg/kg when administered intraperitoneally. TrkC and increases pre and post synaptic proteins and spine density in aged mice[1].
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