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Review
.2018 Nov 19;19(11):3650.
doi: 10.3390/ijms19113650.

Actions of Brain-Derived Neurotrophin Factor in the Neurogenesis and Neuronal Function, and Its Involvement in the Pathophysiology of Brain Diseases

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Review

Actions of Brain-Derived Neurotrophin Factor in the Neurogenesis and Neuronal Function, and Its Involvement in the Pathophysiology of Brain Diseases

Tadahiro Numakawa et al. Int J Mol Sci..

Abstract

It is well known that brain-derived neurotrophic factor, BDNF, has an important role in a variety of neuronal aspects, such as differentiation, maturation, and synaptic function in the central nervous system (CNS). BDNF stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phosphoinositide-3kinase (PI3K), and phospholipase C (PLC)-gamma pathways via activation of tropomyosin receptor kinase B (TrkB), a high affinity receptor for BDNF. Evidence has shown significant contributions of these signaling pathways in neurogenesis and synaptic plasticity in in vivo and in vitro experiments. Importantly, it has been demonstrated that dysfunction of the BDNF/TrkB system is involved in the onset of brain diseases, including neurodegenerative and psychiatric disorders. In this review, we discuss actions of BDNF and related signaling molecules on CNS neurons, and their contributions to the pathophysiology of brain diseases.

Keywords: brain-derived neurotrophic factor; intracellular transport; neurodegeneration; neurogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration of a possible molecular mechanism of selective serotonin reuptake inhibitor (SSRI)- or ketamine-induced antidepressive effect. NCPS: neural progenitor cells; DG: dentate gyrus. Both antidepressants increase BDNF production in hippocampal neurons via distinct pathways and finally increased neurogenesis by stimulating TrkB in NPCs. ↑:Upregulation; ↓:Downregulation; × at NMDAR means blockage of NMDAR; → at BDNF transcription means transcription of BDNF genes.
Figure 2
Figure 2
A proposed model of the bi-directional transport of BDNF/TrkB-containing vesicle on microtubules. The motor complex includes the motor proteins, huntingtin, huntingtin-associated protein 1 (HAP1), and dynactin complex. It can involve both kinesin and dynein simultaneously that are responsible for the anterograde (towards to the plus-end of microtubule) and the retrograde (to the minus-end) transport of cargos, respectively. Phosphorylation of huntingtin at serine 421 is possible to regulate the direction of transport, by stabilizing kinesin at the complex and dominantly move to the plus-end. Dynein-dependent retrograde transport becomes dominant when huntingtin is dephosphorylated (See also [166]). Because impaired intracellular transport of BDNF/TrkB-containing vesicles has been suggested as pathophysiology of neurodegenerative diseases, ameliorating the impairment would be a potential therapeutic target for the future medical treatment. +: plus end; -: minus end.
See this image and copyright information in PMC

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