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Title: Búsqueda de moléculas con potencial terapéutico para la enfermedad de Alzheimer mediante análisis de virtual screening
Author: Ellson Lancho, Ivan
Tutor: Sánchez Martínez, Melchor
Others: Marco-Galindo, Maria-Jesús  
Keywords: virtual screening
Issue Date: 2-Jan-2019
Publisher: Universitat Oberta de Catalunya (UOC)
Abstract: Alzheimer's disease (AD) is the leading neurodegenerative disorder worldwide. Traditionally, research in AD has been based on tau and ß-amyloid hypothesis, but its pathology is complex and has a multifactorial nature. Therefore, here we propose to study two alternative paths related to AD: the leukotriene path and the neuroinflammation by the NLRP3 inflammasome. To do so, we chose four AD-related targets: 5-Lipooxygenase and Leukotriene-C4 Synthase for the leukotriene path, and Cathepsin B and MyD88 protein for the inflammasome path. We hypothesized that, after virtual screening analysis, the molecules found will show potential inhibitory features on the chosen targets. In order to do this, we conducted a docking based virtual screening analysis using a drug-like compound library. The best results were visually checked and compared with actual inhibitors and then we performed the analysis of some molecule properties to check if they could cross the central nervous system (CNS) and the blood-brain barrier (BBB). After virtual screening, we obtained six molecules for each target: R428 for 5-Lox, Lumacaftor for LTC4S, Venetoclax for Cathepsin B, and ZINC118915483, Dihydroergotamine and RAF265 for MyD88 binding sites 1 to 3, respectively. We concluded that all the molecules showed good inhibitory features, although some of them couldn't cross the CNS and BBB by passive transport. Looking forward, we think that these inhibitors are good candidates for future drug design processes, including further improvement of their distribution properties in some cases, in order to become an effective therapy for AD.
Language: Spanish
Appears in Collections:Trabajos finales de carrera, trabajos de investigación, etc.

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