Interactions of Selective Serotonin Reuptake Inhibitors with β-Amyloid

Treating Alzheimer’s disease (AD) is a major challenge at the moment with no new drugs available to cure this devastating neurodegenerative disorder. In this regard, drug repurposing, which aims to determine novel therapeutic usage for drugs already approved by the regulatory agencies, is a pragmatic approach to discover novel treatment strategies. Selective serotonin reuptake inhibitors (SSRIs) are a known class of United States Food and Drug Administration approved drugs used in the treatment of depression. We investigated the ability of SSRIs fluvoxamine, fluoxetine, paroxetine, sertraline, and escitalopram on Aβ42 aggregation and fibrillogenesis. Remarkably, the aggregation kinetic experiments carried out demonstrate the anti-Aβ42 aggregation activity of SSRIs fluoxetine, paroxetine, and sertraline at all the tested concentrations (1, 10, 50, and 100 μM). Both fluoxetine and paroxetine were identified as the most promising SSRIs, showing 74.8 and 76% inhibition of Aβ42 aggregation at 100 μM. The trans...