Targeting TrkB neurotrophin receptor to treat depression

Abstract

Background: An increasing number of findings point out the key role of the BDNF (brain-derived neurotrophic factor) receptor, tyrosine kinase receptor B (TrkB), in the regulation of antidepressant drug actions. Therefore, targeting TrkB receptors might be a rational strategy to develop novel antidepressant drugs. Objective/methods: In this review we will discuss several approaches to targeting the TrkB receptor using existing or novel drugs. We will mainly concentrate on the following issues: i) synthesis, release and cleavage of neurotrophins; ii) augmentation of the actions of neurotrophins; iii) synthesis of TrkB; iv) developing agonists for TrkB; and v) TrkB transactivation. Conclusions: Different molecular approaches can be used to screen antidepressant drugs acting through TrkB receptors but it remains to be seen whether they demonstrate therapeutic antidepressant effects.

Keywords::

• BDNF cleavage
• chromatin remodeling
• pro-BDNF
• p75^NTR receptor
• transactivation
• TrkB agonist
• truncated TrkB receptor

Acknowledgments

The authors would like to thank Dr Olivia F O'Leary for her valuable comments to improve this manuscript. We would also like to thank B.Sci. Henri Autio for making the figure for this manuscript.

Notes