Fig. 2

Interaction between neurotrophins and VEGF. Binding of neurotrophins like BDNF (brain derived growth factor) and NGF (nerve growth factor) to their respective receptors TrkB/A triggers PI-3kinase/AKT/mTOR pathway and leads to increased expression of HIF-1α protein expression. Activated mTOR leads to the phosphorylation and activation of ribosomal protein S6 kinase (p70S6K) which in turn known to regulate HIF-1α expression at the translational level. HIF-1α then dimerizes with HIF-1β to form HIF complex which translocate to the nucleus and binds to hypoxia response elements and leads to the increased transcription of VEGF (vascular endothelial growth factor) in the brain. NGF: Nerve Growth Factor: BDNF: Brain Derived Growth Factor; TrkB/TrkA: Tropomyosin receptor kinase B/A; PI3K: phosphoinositide 3-kinase; Akt: serine/threonine-specific protein kinase also called as protein kinase B; mTOR: mammalian target of rapamycin; HIF-1α: Hypoxia Inducible Factor-α; HIF-1β: Hypoxia Inducible Factor-β; p70S6K: ribosomal protein S6 kinase; VFGF: Vascular Endothelial Growth Factor