Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime?

Figure 1 Brain-derived neurotrophic factor signaling cascade diagram. When TrkB is activated by binding mature brain-derived neurotrophic factor (BDNF), the intracellular domains of the receptor dimerize and autophosphorylate one of three tyrosine residues. Phosphorylation at each residue initiates a distinct signaling cascade: Ras-PI3K-Akt, Ras-MAP kinase-Erk, or phospholipase Cγ. These signaling cascades activate transcription factor CREB, resulting in cell proliferation, cell survival, synaptogenesis, and memory formation. ProBDNF binds to pan-neurotrophin receptor P75^NTR. P75^NTR signaling activates transcription factor NFκB, leading to inflammation and apoptosis. BDNF: Brain-derived neurotrophic factor.