Brain-derived neurotrophic factor-tropomyosin receptor kinase B receptor pathway (BDNF-TrkB pathway)

The Brain-derived neurotrophic factor-tropomyosin receptor kinase B receptor pathway (BDNF-TrkB pathway) is a central neurotrophic signaling mechanism in the nervous system. BDNF is a secreted growth factor that binds the TrkB receptor, a member of the tyrosine kinase receptor family, to promote neuronal growth, survival, maintenance, and synaptic plasticity. Upon BDNF binding, TrkB dimerizes and undergoes autophosphorylation, activating major intracellular cascades—PLCγ, PI3K/Akt, and MAPK/ERK—that regulate gene expression, synaptic function, and neuroprotection. This pathway plays a critical role in cognitive processes, including learning and memory, and is implicated in the pathogenesis of neurodegenerative and psychiatric diseases. Several drugs and biologics target this pathway either by upregulating BDNF expression, directly activating TrkB, or modulating downstream signaling, making it a major focus of therapeutic development for CNS disorders.

Other names

BDNF-TrkB pathwayBDNF/TrkB signalingBrain-derived neurotrophic factor/trkB signalingNTRK2 signalingNeurotrophin pathway

Ligand (BDNF) binding to TrkB triggers receptor dimerization and autophosphorylation. Activation of intracellular signaling pathways: phospholipase-Cγ (PLCγ), phosphatidylinositol 3-kinase (PI3K)/Akt, and mitogen-activated protein kinase (MAPK)/ERK. Promotes neuronal survival through anti-apoptotic signaling. Enhances synaptic plasticity and neurotransmission. Inhibition (antagonists or dominant-negative isoforms like TrkB.T1) suppresses BDNF signaling and impacts survival/plasticity.