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dc.contributor.advisorKristiansen, Kurt
dc.contributor.advisorSylte, Ingebrigt
dc.contributor.authorErnstsen, Maria Leiknes
dc.date.accessioned2016-07-27T09:02:19Z
dc.date.available2016-07-27T09:02:19Z
dc.date.issued2016-05-12
dc.description.abstractThe exposure to pollutants is a serious and increasing health problem, which has been associated with increased morbidity and mortality among people. Many toxic compounds can accumulate in the environment and evidence suggests that most people have varying degrees of toxic compounds within their body. This can result in disruption of many physiological processes in the human body and the development of several central nervous system (CNS) diseases, including Alzheimer’s disease (AD). Glutamate and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters in the human brain, which target both G protein-coupled receptors (GPCRs) and ionotropic receptors. They have important roles in physiological processes and play roles in different CNS diseases, and disruption of their neurotransmission may cause harmful effects in humans. The aim of this study was to use constructed homology models and some resolved X-ray structures of glutamatergic GPCRs and homology models of the GABA transporter 1 (GAT1), in order to predict putative interactions and binding modes of several toxic compounds retrieved from the Toxicology in the 21st Century (Tox21) database. Receptor and transporter models were able to bind several of the toxic compounds, including some drugs. Many of them showed better affinity to the models than their known binders. Toxicants with good affinity to a receptor or transporter can result in adverse effects in humans, where the toxicants can outperform several endogenous and exogenous binders. Further studies should involve in vitro assays to investigate the binding of toxicants, and especially those that have the ability to cross the blood brain barrier (BBB).en_US
dc.identifier.urihttps://hdl.handle.net/10037/9493
dc.identifier.urnURN:NBN:no-uit_munin_9051
dc.language.isoengen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.rights.accessRightsopenAccess
dc.rights.holderCopyright 2016 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)en_US
dc.subject.courseIDFAR-3911
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Pharmacology: 728en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Toksikologi: 730en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Toxicology: 730en_US
dc.titleModeling of glutamatergic and GABAergic drug targets in the CNS and their interactions with environmental toxicantsen_US
dc.typeMaster thesisen_US
dc.typeMastergradsoppgaveen_US


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Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)