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. 2022 Jan 19;12(1):77–97. doi: 10.5498/wjp.v12.i1.77

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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

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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.