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

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

CaMKIV mediates spine growth deficiency of hippocampal neurons by regulation of EGR3/BDNF signal axis in congenital hypothyroidism

“…The neurotrophin BDNF plays an essential role in brain development and regular physiological activity [64]. Dysregulation of BDNF influences neurite development, synapse formation, and stabilization of CNS neurons, which are associated with multiple diseases of CNS, even postnatal death [65][66][67].…”

Neurotrophic basis to the pathogenesis of depression and phytotherapy

“…BDNF, primarily synthesized in neurons, is ubiquitously distributed throughout the central nervous system (CNS). It is involved in the repair of synaptic plasticity, the transduction of 5-hydroxytryptamine (5-HT) signaling, and the level of 5-HT in the brain ( Bhattarai et al, 2020 ; Costa et al, 2022 ). Consistent reports have certified that BDNF is associated with the occurrence, development, and management of depression, and it has received the most attention in the neurobiology of depression among any neurotrophic factors.…”

RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration

“…The CPEB is also involved, in the hippocampus, in the transport of the mRNA encoding the brain-derived neurotrophic factor (BDNF), which bears a specific dendritic targeting element in its 3′-UTR. In the dendritic transport of this mRNA, the protein Translin also seems to be involved [ 113 , 114 ]. After transport along microtubules, RNPs can be transferred to the peripheral actin cytoskeleton, thus penetrating the dendritic spines; in this transfer, Fused in Sarcoma (FUS) RBP can be involved, thanks to its ability to interact with the myosin-Va motor protein [ 115 ].…”

“…The structuration and function of mature synapses is influenced by local translation depending on BDNF–TrkB signaling. Trk receptors are indeed widespread both in the presynaptic and postsynaptic density of the dendritic spines of cortical neurons [ 114 ]. For a long time, BDNF neurotrophin was supposed to be synthesized just in the cell body, then transported along the axon and secreted.…”

“…BDNF induces the dephosphorylation of the FMRP, through a mechanism depending on Calcineurin. In this way, BDNF enhances the translation of a set of transcripts binding to the FMRP (reviewed in [ 114 ]). BDNF mRNA is also transported to dendrites, and some authors reported a role for Translin in the process [ 113 ].…”