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. 2022 Jul 13;23(14):7726. doi: 10.3390/ijms23147726

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Neurotrophins, receptors, and intracellular signaling. (A) Neurotrophins consist of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Each neurotrophin has high affinity receptor; NGF binds to TrkA, BDNF and NT-4 to TrkB, and NT-3 to TrkC. In addition, all neurotrophins bind to p75NTR with low affinity. Mature (processed) neurotrophin is firstly translated as a precursor proneurotrophin which has high affinity for p75NTR. (B) Activation of TrkB stimulated by BDNF triggers downstream intracellular signaling pathways (mainly, PI3K/Akt, ERK, and phospholipase Cγ (PLCγ) contributes to positive regulation of cell differentiation, survival, synaptic function, and neurogenesis. p75NTR-mediated signaling is involved in negative regulation of cell survival and synaptic function. Truncated isoform TrkB.T1 exerts a dominant-negative role against the function of full-length TrkB or a BDNF scavenging effect in the CNS.