Efavirenz and Fexofenadine ameliorates the propagation of alpha-synuclein

Current treatments for Parkinson's disease include drug therapy with L-DOPA and MAO-A inhibitors, as well as surgical methods like deep brain stimulation, which can delay disease progression but are not curative. Numerous clinical trials are underway for the development of new drugs, but no approved drugs exist yet. In this study, a list of drugs that included efavirenz and fexofenadine was provided through deep learning. Using these drugs, it was found that they can alleviate the propagation of alpha-synuclein and reduce neuroinflammation in vitro models, in vivo mice, and C.elegans models. RNA-seq and IPA analyses revealed that efavirenz has an effect through the activation of CYP46A1 and the regulation of cholesterol metabolism. also, fexofenadine has an effect inflammation via regulating infiltrated peripheral immune cells. This study not only sheds light on the mechanism of propagation in Parkinson's disease but also suggests the potential use of efavirenz and fexofenadine as a potential treatment for Parkinson's disease through drug repurposing. To investigate the mechanisms of efavirenz, we performed an animal experiment in which we treated the striatum of M83 alpha-synuclein A53T Tg mice with 10 μg of alpha-synuclein PFF and administered efavirenz or fexofenadine for 4 weeks. Subsequently, we extracted RNA from the cortex and performed RNA-seq.