Brain-derived neurotrophic factor signaling pathway (BDNF signaling)

The Brain-derived neurotrophic factor (BDNF) signaling pathway is a fundamental regulator of neuronal growth, survival, and plasticity in the mammalian nervous system (Huang & Reichardt, 2001, PMID: 11252354). BDNF exerts its primary biological effects by binding to the high-affinity Tropomyosin receptor kinase B (TrkB), which triggers downstream intracellular cascades including the PI3K/Akt, MAPK/ERK, and PLCγ pathways (UniProt P23560, Q16620). These cascades are essential for long-term potentiation, synaptic strengthening, and the maintenance of cognitive functions. Deficiencies in BDNF signaling are strongly implicated in the pathophysiology of various neuropsychiatric and neurodegenerative disorders, such as major depressive disorder and Alzheimer's disease (Autry & Monteggia, 2012, PMID: 22252337). Consequently, the pathway is a major focus for drug development, with strategies ranging from direct TrkB agonists like 7,8-dihydroxyflavone to indirect modulators like ketamine that enhance endogenous BDNF levels (Jang et al., 2010, PMID: 20308554). However, therapeutic development faces significant challenges, including poor blood-brain barrier penetration and potential metabolic side effects due to the pathway's role in energy homeostasis and satiety.

Other names

BDNF-TrkB signaling pathwayNeurotrophin signaling pathwayBDNF/TrkB axis

Activation of the Tropomyosin receptor kinase B (TrkB) receptor, modulation of the p75 neurotrophin receptor (p75NTR), and enhancement of endogenous BDNF expression or release to trigger downstream PI3K/Akt, MAPK/ERK, and PLCγ cascades.