5-HTR2B and SLC6A3 as potential molecular targets of sertraline in the treatment of major depressive disorder: the use of bioinformatics and its practical implication

AbstractMajor depressive disorder (MDD) is known to be a highly limiting and disabling disorder worldwide. The main management for this disorder is based on pharmacological therapy with antidepressants, especially in moderate to severe presentations. Among these, selective serotonin reuptake inhibitors (SSRIs) are, at the moment, the most widely prescribed class. Individualized pharmacological therapy presents itself as a powerful tool to reduce the course of the disorder, especially if one takes into account the potential molecular targets and the relationship of these targets in MDD pharmacotherapy. To explore this possibility, using bioinformatics approaches, we combined two reverse molecular screening approaches, followed by traditional docking simulations to identify potential molecular targets specifically for sertraline. According to our results, sertraline presented 17 potential targets, 4 in common within both inverse screening approaches, and were analyzed in our study: 5-HTR2B (5-hydroxytryptamine receptor 2B subtype), SLC6A2 (norepinephrine transporter), SLC6A3 (dopamine transporter) and SLC6A4 (serotonin transporter). Traditional docking simulations revealed higher interaction energies of 5-HTR2B and SLC6A3 with the sertraline molecule. In addition, both proteins are directly or indirectly related to the modulation of serotonin and dopamine, as well as the rate of response to SSRIs. Therefore, we suggest that the interaction of sertraline with the 5-HTR2B and SLC...
Source: Network Modeling Analysis in Health Informatics and Bioinformatics - Category: Bioinformatics Source Type: research