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An activator of TrkB and TrkC
LM22B-10 is an activator of neurotrophic tyrosine kinase receptor 2 (TrkB) and -3 (TrkC).1 It is selective for TrkB and TrkC over TrkA in NIH3T3 cells but does inhibit the serotonin (5-HT) receptor subtype 5-HT5A and the dopamine transporter by greater than 50% in a panel of 57 G protein-coupled peptide and nonpeptide receptors at 10 ?M. LM22B-10 increases survival, neurite length, and dendritic spine density of primary mouse embryonic hippocampal neurons when used at a concentration of 1 ?M. LM22B-10 (50 mg/kg i.p. in combination with an intranasal dose of 5 mg/kg per day) also increases hippocampal neuron dendritic spine density in aged mice.
1.Yang, T., Massa, S.M., Tran, K.C., et al.A small molecule TrkB/TrkC neurotrophin receptor co-activator with distinctive effects on neuronal survival and process outgrowthNeuropharmacology110(Pt A)343-361(2016)
Cell experiment: |
Mouse NIH-3T3 cells, mouse NIH-3T3 cells expressing TrkA (NIH-3T3-TrkA) or p75NTR (NIH-3T3-p75NTR), and NIH-3T3 cells expressing TrkB (NIH-3T3-TrkB) or TrkC (NIH-3T3-TrkC) are propagated in DMEM supplemented with 10% FBS and 200-400 μg/mL Geneticin (for Trk-expressing cells) or 400 μg/mL hygromycin (for p75NTR-expressing cells). Cells are seeded into 24-well plates (30,000 cells/well) and cultured in medium consisting of 50% PBS and 50% DMEM without supplements. Following exposure to growth factors (0.7 nM) or 1000 nM LM22B-10 for 72-96 h, cells are suspended in 50 μL lysis buffer, transferred to opaque 96-well culture plates and survival is measured using the ViaLight Assay. |
参考文献: [1]. Yang T, et al. A small molecule TrkB/TrkC neurotrophin receptor co-activator with distinctive effects on neuronal survival and process outgrowth. Neuropharmacology. 2016 Nov;110(Pt A):343-61. |
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