Tropomyosin receptor kinase B (TrkB) (TrkB)

Tropomyosin receptor kinase B (TrkB), also known as NTRK2, is a member of the receptor tyrosine kinase family and serves as the primary functional receptor for brain-derived neurotrophic factor (BDNF) [2, 18]. It is predominantly expressed in the central and peripheral nervous systems, where it plays a critical role in neuronal development, survival, and the regulation of synaptic plasticity [8, 11]. Upon activation by BDNF or neurotrophin-4, TrkB undergoes homodimerization and autophosphorylation, initiating intracellular signaling through the PI3K/Akt, MAPK/ERK, and PLCγ pathways [9, 18]. These cascades are essential for processes such as long-term potentiation, memory formation, and dendritogenesis [2, 19]. In pathology, impaired TrkB signaling is a hallmark of neurodegenerative conditions like Alzheimer's disease and psychiatric disorders such as major depressive disorder [1, 13, 20]. Conversely, oncogenic activation of TrkB, often through gene fusions or overexpression, drives the progression of various solid tumors and neurogenic cancers [3, 7, 8]. Therapeutic strategies targeting TrkB include the use of small-molecule inhibitors like larotrectinib for NTRK-fusion positive malignancies and the development of agonists or allosteric modulators to treat neurological and psychiatric conditions [8, 10, 14].

Other names

NTRK2Neurotrophic receptor tyrosine kinase 2BDNF/NT-3 growth factors receptorTrk-BGP145-TrkBObesity-associated protein (OBHD)Tyrosine receptor kinase B

Competitive inhibition of the ATP-binding site (for inhibitors); Receptor agonism via the extracellular domain (for agonists); Positive allosteric modulation of the transmembrane domain (for modulators like antidepressants).