Brain-derived neurotrophic factor signaling pathway (BDNF signaling pathway) (BDNF pathway)

The Brain-derived neurotrophic factor (BDNF) signaling pathway is a fundamental neuroprotective mechanism in the central nervous system, primarily driven by the interaction between the neurotrophin BDNF and its high-affinity receptor, Tropomyosin receptor kinase B (TrkB) [1, 3]. Upon activation, TrkB triggers downstream cascades including PI3K/Akt, MAPK/ERK, and PLCγ, which are essential for neuronal survival, synaptic plasticity, and neurogenesis [2, 10]. This pathway is critical for cognitive functions such as learning and memory, and its impairment is strongly linked to the pathogenesis of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as psychiatric conditions like major depression [2, 15]. Therapeutic interventions focus on enhancing this pathway through TrkB agonists, allosteric modulators, or drugs that increase endogenous BDNF levels, such as antidepressants and ketamine [6, 11, 13]. However, the pathway also involves the precursor proBDNF, which can promote apoptosis through the p75 neurotrophin receptor (p75NTR), adding a layer of complexity to its therapeutic modulation [8, 15].

Other names

BDNF-related neuroprotective pathwaysBDNF/TrkB signaling pathwayNeurotrophin signaling pathwayBDNF signaling axis

Activation of the Tropomyosin receptor kinase B (TrkB) by Brain-derived neurotrophic factor (BDNF) induces receptor dimerization and autophosphorylation of intracellular tyrosine residues. This process recruits adapter proteins that trigger three major signaling cascades: the PI3K/Akt pathway, which promotes neuronal survival; the MAPK/ERK pathway, which regulates differentiation and synaptic plasticity; and the PLCγ pathway, which modulates synaptic transmission and calcium homeostasis [1, 2, 10].