Description du projet
Une enzyme pour combattre les maladies du foie
L’incidence croissante de l’obésité et du diabète de type II a contribué à une très forte prévalence de la stéatose hépatique non alcoolique (SHNA), une maladie incurable. Affectant désormais une personne sur quatre en Europe, la SHNA peut évoluer vers une cirrhose et un cancer du foie. Elle est également associée à un risque accru de maladies cardiovasculaires et d’autres tumeurs malignes. Une enzyme naturellement présente dans le corps peut jouer un rôle dans l’arrêt de la progression de la maladie. Le projet Food-PPP-NAFLD utilise des méthodes de haute technologie pour étudier de nouveaux composés alimentaires bioactifs et des agents pharmacologiques préalablement identifiés qui renforcent l’activité de cette molécule. Les résultats de la recherche ajouteront de nouvelles connaissances sur les voies biochimiques impliquées dans les maladies métaboliques.
Objectif
Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults, and at present there is no approved licensed medication. Oxidative stress has been recognised as an important factor in the pathological progression of NAFLD. Therefore, therapies to protect against liver redox imbalance in the progression of this disease are urgently needed. G6PD is the rate-limiting enzyme of the pentose phosphate pathway (PPP), providing the majority of the cellular NADPH necessary for most antioxidant enzymes. The host group is specialized in nutritional interventions, metabolism and associated pathologies. They have recently demonstrated that increased levels of NADPH, induced by a moderate and regulated overexpression of G6PD, protected against aging-associated ROS oxidative damage in mice. This, in combination with the experience of the applicant in the prevention of NAFLD by using bioactives compounds, create an outstanding context for the Action. This new Marie-Skłodowska-Curie Action will explore the role of G6PD in the prevention or treatment of NAFLD. Technically, a new high-throughput screening platform will be set up to discover and characterise new food bioactive compounds modulating G6PD activity. The new bioactive compounds, as well as previously characterized pharmacological agonists/antagonists of G6PD, will be tested and validated in mouse models of NAFLD, and the mechanisms of action will be assessed using different in vitro and in vivo approaches. This Action will give further insight into the novel concept of the role of the PPP in the field of metabolic diseases, almost unexplored up to date. In addition, it will encompass a very inter-disciplinary approach including the fields of Food Science and Technology, Biomedicine and Molecular Biology, establishing collaborations with different research groups. In all, this Action will constitute a conceptual advance in the field, and will become an optimal scenario for the career development of the applicant.
Champ scientifique
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesbasic medicinepathology
- medical and health sciencesclinical medicinehepatology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
- natural sciencesbiological sciencesmolecular biology
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
28049 Madrid
Espagne