Objectif The main purpose of this computational research is to improve the understanding of a relation between features, metabolic pathways and signal transduction of amine neurotransmitters and the treatment of neurological diseases. Brain monoaminergic systems have been extensively implicated in the etiology and course of various neurodegenerative disorders, and their binding proteins such as receptors, transporters and common metabolic enzymes are the starting points for development of tools to diagnose and drugs to treat specific clusters of symptoms. Therefore, the research described here will be focused on two particular biological systems: monoamine oxidase enzymes (MAOs) responsible for regulating amine levels in the synaptic region, and histamine H1 and H2 receptors that regulate the activity of allergic and inflammatory mediator histamine. The work on MAO should aid in revealing molecular mechanisms of MAO-catalyzed amine degradation to their corresponding aldehydes, as well as of irreversible MAO inhibition related to the pharmacotherapy of depression, Parkinson disease and age-related cognitive disorders. This should help improve efficiency and reduce adverse effects of commercially available drugs, and should suggest novel classes of active compounds as transition state analogues. In joint computational/experimental efforts, studies on histamine receptors should unlock the secrets of receptor's distinction between agonist and antagonist binding using receptor deuteration, being of major relevance for molecular pharmacology. Overall, it is intended to identify ubiquitous trends and features that are applicable well beyond the scopes of these individual investigations. The proposed research is in general highly interdisciplinary with the promise of industrial applications, since it bridges the gap between fundamental understanding of biological systems and preclinical medicine combining modern methods of computational biochemistry with pharmacological approaches. Champ scientifique natural scienceschemical sciencesorganic chemistryaldehydesmedical and health sciencesbasic medicineneurologyparkinsonnatural scienceschemical sciencesorganic chemistryaminesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesmedical and health sciencesbasic medicinepharmacology and pharmacy Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2012-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur RUDER BOSKOVIC INSTITUTE Contribution de l’UE € 100 000,00 Adresse Bijenicka cesta 54 10000 Zagreb Croatie Voir sur la carte Région Hrvatska Grad Zagreb Grad Zagreb Type d’activité Research Organisations Contact administratif Marijana Klasnić Kožar (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée