Targeting TrkB neurotrophin receptor to treat depression

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.

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.

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.