Brain-derived neurotrophic factor-Tropomyosin receptor kinase B complex (BDNF-TrkB) (BDNF-TrkB)

The Brain-derived neurotrophic factor-Tropomyosin receptor kinase B (BDNF-TrkB) complex is a fundamental signaling unit in the central and peripheral nervous systems, primarily responsible for mediating neuronal survival, differentiation, and synaptic plasticity [1, 6]. Upon the binding of the dimeric BDNF ligand to the extracellular domain of the TrkB receptor, the complex undergoes dimerization and trans-autophosphorylation of tyrosine residues in the cytoplasmic tail [1, 13]. This activation triggers several intracellular signaling cascades, including the PI3K/Akt, Ras/MAPK, and PLCγ pathways, which are essential for cognitive processes such as long-term potentiation and memory formation [1, 9]. Dysregulation of the BDNF-TrkB complex is a hallmark of various neurological and psychiatric conditions, including major depressive disorder, Alzheimer's disease, and Parkinson's disease, where signaling is often diminished [10, 11, 14]. Conversely, in oncology, the BDNF-TrkB axis can function as an oncogenic driver, promoting tumor cell proliferation, survival, and metastasis in cancers such as neuroblastoma and lung carcinoma [3, 8]. Therapeutic interventions target this complex through various modalities: TrkB agonists and positive allosteric modulators (including traditional antidepressants like fluoxetine and rapid-acting agents like ketamine) are used to enhance neuroplasticity, while Trk inhibitors are employed as potent anti-cancer therapies [3, 4, 5].

Other names

BDNF/NTRK2 complexBDNF/TrkB signaling pathwayBDNF-TrkB receptor systemBrain-derived neurotrophic factor-Neurotrophic receptor tyrosine kinase 2 complexTrkB-BDNF complex

The complex is targeted via agonism and positive allosteric modulation to enhance neurotrophic signaling in neurodegenerative and psychiatric disorders, or via antagonism and tyrosine kinase inhibition to suppress oncogenic signaling in various cancers [3, 4, 5, 11].