{"id":71841,"date":"2018-03-09T23:16:34","date_gmt":"2018-03-09T23:16:34","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/senalizacion-adrenergica-en-la-enfermedad-de-alzheimer-asociacion-de-los-polimorfismos-de-los-genes-adrb1-y-gnb3\/"},"modified":"2018-03-09T23:16:34","modified_gmt":"2018-03-09T23:16:34","slug":"senalizacion-adrenergica-en-la-enfermedad-de-alzheimer-asociacion-de-los-polimorfismos-de-los-genes-adrb1-y-gnb3","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/senalizacion-adrenergica-en-la-enfermedad-de-alzheimer-asociacion-de-los-polimorfismos-de-los-genes-adrb1-y-gnb3\/","title":{"rendered":"Se\u00f1alizaci\u00f3n adren\u00e9rgica en la enfermedad de alzheimer. asociaci\u00f3n de los polimorfismos de los genes adrb1 y gnb3."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Mar\u00eda  Del Carmen Ramos Martin <\/strong><\/h2>\n<p>Para investigar el papel de la se\u00f1alizaci\u00f3n adren\u00e9rgica en la enfermedad de alzheimer (ea), generamos una serie de estudios gen\u00e9ticos y funcionales de los genes iniciadores de la cascada adren\u00e9rgica. Seleccionamos dos polimorfismos de cambio de una sola base (snps): en el gen del receptor beta1-adren\u00e9rgico (adrb1) y  en el de la subunidad beta3 de las prote\u00ednas g heterotrim\u00e9ricas (gnb3) y analizamos sus frecuencias al\u00e9licas en un estudio caso-control para la ea. Encontramos que el alelo gnb3 t produce un aumento significativo del riesgo para la ea en los individuos homocigotos para el alelo adrb1 c, sugiriendo que el efecto combinado de ambos influye sobre la susceptibilidad a la ea. Result\u00f3 interesante encontrar adem\u00e1s que la coexpresi\u00f3n de los alelos adrb1 c y gnb3 t , comparados con los alelos adrb1 g y gnb3 c, produc\u00edan un aumento de la cantidad de camp, de la activaci\u00f3n de mapk-erk1\/2 y del factor de transcripci\u00f3n creb tras estimulaci\u00f3n adren\u00e9rgica en l\u00edneas celulares humanas transfectadas. Adem\u00e1s, la coexpresi\u00f3n de los alelos de riesgo tambi\u00e9n aument\u00f3 la expresi\u00f3n de la prote\u00edna precursora del p\u00e9ptido  beta-amiloide (app). Usamos tambi\u00e9n experimentos de uni\u00f3n de radioligandos para descartar que existieran diferencias en la afinidad por el agonista adren\u00e9rgico isoproterenol entre las dos variantes del receptor.  en segundo lugar encontramos que la isoforma 389arg del receptor, codificada por el alelo adrb1 c, posee una mayor afinidad por el agonista inverso betaxolol y que las c\u00e9lulas de neuroblastoma transfectadas establemente con la combinaci\u00f3n de los alelos de riesgo alcanzan un mayor grado de desensibilizaci\u00f3n respecto a las c\u00e9lulas transfectadas con las respectivas par\u00e9jas al\u00e9licas.  realizamos adem\u00e1s, un an\u00e1lisis de la expresi\u00f3n g\u00e9nica de la l\u00ednea de neuroblastoma tras estimulaci\u00f3n adren\u00e9rgica que mostr\u00f3 cambios en numerosos genes implicados en la se\u00f1alizaci\u00f3n, la oncog\u00e9nesis y el<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Se\u00f1alizaci\u00f3n adren\u00e9rgica en la enfermedad de alzheimer. asociaci\u00f3n de los polimorfismos de los genes adrb1 y gnb3.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Se\u00f1alizaci\u00f3n adren\u00e9rgica en la enfermedad de alzheimer. asociaci\u00f3n de los polimorfismos de los genes adrb1 y gnb3. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Mar\u00eda  Del Carmen Ramos Martin <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 14\/12\/2004<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Fernando Valdivieso Amate<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: jorgina Satr\u00fastegui gil-delgado <\/li>\n<li>margarita Lorenzo balado (vocal)<\/li>\n<li>Manuel Ros perez (vocal)<\/li>\n<li> Artiga gonz\u00e1lez Mar\u00eda Jes\u00fas (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Mar\u00eda Del Carmen Ramos Martin Para investigar el papel de la se\u00f1alizaci\u00f3n adren\u00e9rgica en la enfermedad de [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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