NTRK2

Neurotrophic tyrosine receptor kinase 2 (NTRK2), also known as TrkB or BDNF/NT-3 growth factors receptor, is a transmembrane receptor tyrosine kinase activated by brain-derived neurotrophic factor (BDNF). It regulates neuronal survival, differentiation, and synaptic plasticity through ligand-dependent dimerization and autophosphorylation, initiating downstream signaling cascades including MAPK/ERK, PI3K-AKT, and PLCγ pathways. Dysregulation of NTRK2 is implicated in neurodegenerative disorders (e.g., Alzheimer's disease, Huntington's disease), psychiatric conditions (depression, anxiety), and cancers through gene fusions or overexpression. TRK inhibitors such as entrectinib and larotrectinib have received FDA approval for NTRK fusion-positive solid tumors, though acquired resistance mutations (e.g., NTRK2 G595R) remain challenging. Next-generation inhibitors (selitrectinib, repotrectinib) targeting solvent-front mutations are under clinical evaluation. Non-oncological applications targeting BDNF/TrkB signaling are being explored for cognitive enhancement and neuroprotection.