UMYMFOR   05516
UNIDAD DE MICROANALISIS Y METODOS FISICOS EN QUIMICA ORGANICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Study of the molecular basis of steroidal ligands in modulating activity in DAF-12 and LXR nuclear receptors
Autor/es:
ALVAREZ, LAUTARO D.; ARROYO MAÑEZ, PAU; ESTRÍN, DARIO A.; BURTON, GERARDO
Lugar:
Salta
Reunión:
Congreso; 3rd Latin American Protein Society Meeting and XXXIX Annual Meeting of the Argentinian Biophysical Society; 2010
Institución organizadora:
Latin American Protein Society y Sociedad Biofísica Argentina
Resumen:
Nuclear Receptors (NR) are a superfamily of receptors acting as transcription factors that can be activated or supressed by the presence of ligands. The NRs perform many functions in the organism, such as the embriogenic development, metabolism and cell death.[1] Recent studies point to an involvement of the NRs in the aging process. The Caenorhabditis elegans nematode has the DAF-12 NR (ceDAF12) which regulates its response to adverse conditions.[2] This protein is involved in the switching to an alternative state of diapause characterized by a decrease in aging velocity, as well as in many processes related with its resistance to stress and life span.[3] Reciently, Mooijaart et al. found the human LXRa receptor to be the NR with highest sequence similarity in the Ligand Binding Pocket (LBP) to the DAF-12. They also observed that mutations in the gene that codifies for this receptor are related with human life expectation.[4-5] Ligand binding to LXR is related to an increase in catabolism and excretion of cholesterol, determinants of mortality in the elderly. In adition, the LXRb isoform was found in high levels during human brain developement. It is known that both DAF-12 and LXR receptors are activated by steroidal ligands structuraly related to cholesterol. Our research group has been working for several years designing selective agonists and antagonists of steroidal hormones, and neuroactive steroids. This project is focused in finding new selective modulators of LXR and DAF12 through a multidisciplinary point of view. A part of this, is the understanding of the molecular basis of these ligands in modulating the NRs activity