LM22B-10 (0.5 mg/kg) activates TrkB, TrkC, AKT and ERK in C57BL/6J mice. LM22B-10 (50 mg/kg, i,p,) shows increased phosphorylation at TrkBY817 and TrkCY820. LM22B-10 activates synaptic TrkB and TrkC and increases pre- and post-synaptic proteins and spine density in aged mice[1].
In Vitro
LM22B-10 exhibits maximum neurotrophic survival activity levels that are higher than those maximally achieved with BDNF (53 ± 7.2% above BDNF at 0.7 nM) and NT-3 (91 ± 8.6% above NT-3 at 0.7 nM) with an EC50 value of 200-300 nM. LM22B-10 (1000 nM) induces neurites of significantly larger average lengths, up to -40 μM. LM22B-10 (250-2000 nM) binds to TrkB-Fc and TrkC-Fc in a dose-dependent manner. LM22B-10 inhibits binding of BDNF to TrkB-expressing cells and NT-3 to TrkC-expressing cells. LM22B-10 promotes cell survival and functions preferentially through TrkB and TrkC. LM22B-10, but not BDNF or NT-3, promotes neurite outgrowth in an inhibitory environment. LM22B-10 induces patterns of Trk and downstream signaling activation that are distinct from those of BDNF and NT-3. LM22B-10 also induces TrkB, TrkC, AKT and ERK activation in hippocampal neurons in culture[1].
Kinase Assay
Cell Assay
Animal Administration
References
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