Brain-derived neurotrophic factor-induced regulation of RNA metabolism in neuronal development and synaptic plasticity

Wiley Interdiscip Rev RNA. 2022 Sep;13(5):e1713. doi: 10.1002/wrna.1713. Epub 2022 Jan 24.

Abstract

The neurotrophin brain-derived neurotrophic factor (BDNF) plays multiple roles in the nervous system, including in neuronal development, in long-term synaptic potentiation in different brain regions, and in neuronal survival. Alterations in these regulatory mechanisms account for several diseases of the nervous system. The synaptic effects of BDNF mediated by activation of tropomyosin receptor kinase B (TrkB) receptors are partly mediated by stimulation of local protein synthesis which is now considered a ubiquitous feature in both presynaptic and postsynaptic compartments of the neuron. The capacity to locally synthesize proteins is of great relevance at several neuronal developmental stages, including during neurite development, synapse formation, and stabilization. The available evidence shows that the effects of BDNF-TrkB signaling on local protein synthesis regulate the structure and function of the developing and mature synapses. While a large number of studies have illustrated a wide range of effects of BDNF on the postsynaptic proteome, a growing number of studies also point to presynaptic effects of the neurotrophin in the local regulation of the protein composition at the presynaptic level. Here, we will review the latest evidence on the role of BDNF in local protein synthesis, comparing the effects on the presynaptic and postsynaptic compartments. Additionally, we overview the relevance of BDNF-associated local protein synthesis in neuronal development and synaptic plasticity, at the presynaptic and postsynaptic compartments, and their relevance in terms of disease. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Export and Localization > RNA Localization.

Keywords: RNA binding proteins; brain-derived neurotrophic factor; intracellular signaling; local protein synthesis; neuronal development; synaptic plasticity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor* / genetics
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Brain-Derived Neurotrophic Factor* / pharmacology
  • Neuronal Plasticity / physiology
  • RNA / metabolism
  • Receptor, trkB* / metabolism
  • Receptor, trkB* / pharmacology
  • Synapses / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • RNA
  • Receptor, trkB