Brain-derived neurotrophic factor pathway components (BDNF pathway)

The Brain-derived neurotrophic factor (BDNF) pathway is a fundamental signaling network in the nervous system that regulates neuronal survival, differentiation, and synaptic plasticity (NIH, 2024). The pathway primarily involves the neurotrophin BDNF and its two receptors: the high-affinity Tropomyosin receptor kinase B (TrkB) and the low-affinity p75 neurotrophin receptor (p75NTR) (Wikipedia, 2024). Activation of TrkB by mature BDNF triggers intracellular cascades, including the PI3K/Akt, MAPK/ERK, and PLC-gamma pathways, which are essential for long-term potentiation and cognitive function (MDPI, 2024). Conversely, the precursor pro-BDNF interacts with p75NTR to facilitate long-term depression or programmed cell death (NIH, 2022). Dysregulation of BDNF signaling is implicated in a wide range of conditions, such as major depressive disorder, Alzheimer's disease, and Huntington's disease (ResearchGate, 2024). Therapeutic interventions include TrkB agonists, BDNF mimetics, and drugs that increase endogenous BDNF expression, though challenges such as blood-brain barrier permeability and off-target effects remain significant (NIH, 2024).

Other names

BDNF/TrkB signaling pathwayNeurotrophin signaling pathwayBDNF-TrkB-p75NTR axisBrain-derived neurotrophic factor signaling

The mechanism of action for drugs targeting this pathway includes TrkB receptor agonism (e.g., 7,8-dihydroxyflavone), TrkB receptor antagonism (e.g., ANA-12), induction of endogenous BDNF expression (e.g., SSRIs, ketamine), and inhibition of Trk kinase activity (e.g., entrectinib) (NIH, 2024; MDPI, 2024).