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. 2015 Dec 11;11(6):1164–1178. doi: 10.5114/aoms.2015.56342

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Copyright © 2015 Termedia & Banach

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

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Signaling pathway of BDNF. BDNF binds to its high-affinity receptor tyrosine kinase B (TrkB), resulting in the recruitment of proteins that activate three different signal transduction cascades. One cascade involves sequential activation of insulin receptor substrate-1 (IRS-1/2), phosphatidylinositol-3-kinase (PI-3K) and protein kinase B (Akt). The second is the activation of Shc/Grb2, Ras, Raf, mitogen-activated protein kinase kinases (MEKs) and extracellular signal regulated kinases (ERKs). The third cascade involves phospholipase C (PLC), inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3], diacylglycerol (DAG) and protein kinase C (PKC). BDNF signaling pathways activate one or more transcription factors (cAMP-response-element-binding protein (CREB) and CREB-binding protein (CBP) that regulate expression of genes encoding proteins involved in neural plasticity, stress resistance and cell survival. This figure is adapted and modified from refs. [32] and [33]