Abstract 2436 Molecular Interactions of SERT and Escitalopram in Serotonin Modulation

Depression is a major public health problem that affects 5% of adults worldwide.1 Depression is commonly treated through Selective Serotonin Reuptake Inhibitors (SSRIs), a category of antidepressants that elevates serotonin levels in the brain. Serotonin, also known as 5-hydroxytryptamine, is a neurotransmitter that plays a critical role in mood regulation.2 Serotonin levels are regulated by controlling the activity of serotonin transporters (SERT), which recycle serotonin molecules back into the presynaptic cell, terminating transmission until the next action potential. SERT employs sodium and chloride ion electrochemical gradients to facilitate the reuptake of serotonin from the synaptic cleft by transporting bound serotonin molecules across the cell membrane through a conformational change.3 SSRIs inhibit the normal functions of SERT protein by either binding to the active or the allosteric site. The Governor's Academy SMART team investigated SERT's mechanism of serotonin transport and molecular interaction with SSRIs, specifically escitalopram, one of the most widely prescribed antidepressants. With support from 3D Molecular Designs, we designed and printed a 3D model that highlights regions important to SERT function and SSRI efficacy. Continued research on SSRIs may lead to the development of newer and more effective treatments for depression. [1] World Health Organization. (2023, March 31). Depressive disorder (depression). WHO. https://www.who.int/news-room/fact-sheets/detail/depression#:∼:text=Globally%2C%20an%20estimated%205%25%20of,mild%2C%20moderate%20and%20severe%20depression. [2] De Deurwaerdère, P., & Di Giovanni, G. (2020). Serotonin in Health and Disease. International journal of molecular sciences, 21(10), 3500. https://doi.org/10.3390/ijms21103500 [3] Yang, D., & Gouaux, E. (2021). Illumination of serotonin transporter mechanism and role of the allosteric site. Science advances, 7(49), eabl3857. https://doi.org/10.1126/sciadv.abl3857.