Gambogic amide selectively upregulates TrkA expression and triggers its activation

BackgroundGambogic amide is the first identified small molecular agonist for TrkA receptor. It mimics NGF functions by selectively activating TrkA receptor and preventing neuron death. However, its function different from that of NGF remains unknown.MethodsIn the current study, we detect the effect of gambogic amide on TrkA expression using TrkA-expressing cell lines in vitro and hippocampi from mice treated with gambogic amide.ResultsWe have confirmed that gambogic amide displays robust neurotrophic activities in provoking neurite outgrowth in vitro. However, gambiogic amide displays a different kinetics from NGF in activating TrkA signals. NGF swiftly provokes TrkA activation and quickly induces TrkA degradation, while gambogic amid selectively upregulates TrkA protein and mRNA levels in a time-dependent manner. Administration of this compound in mice also activates TrkA receptor in hippocampus and promotes TrkA transcription and expression.ConclusionThis study provides a novel mechanism of how gambogic amide regulates TrkA receptor, other than mimicking NGF in triggering TrkA activation.