{"id":12462,"date":"2018-03-09T08:58:19","date_gmt":"2018-03-09T08:58:19","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/regulacion-del-gen-de-la-proteina-precursora-del-peptido-beta-amilode-por-acido-retinoico-y-bdnf-mecanismos-de-accion-y-vias-de-senalizacion-implicadas\/"},"modified":"2018-03-09T08:58:19","modified_gmt":"2018-03-09T08:58:19","slug":"regulacion-del-gen-de-la-proteina-precursora-del-peptido-beta-amilode-por-acido-retinoico-y-bdnf-mecanismos-de-accion-y-vias-de-senalizacion-implicadas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/regulacion-del-gen-de-la-proteina-precursora-del-peptido-beta-amilode-por-acido-retinoico-y-bdnf-mecanismos-de-accion-y-vias-de-senalizacion-implicadas\/","title":{"rendered":"Regulaci\u00f3n del gen de la proteina precursora del peptido beta-amilode por acido retinoico y bdnf; mecanismos de accion y vias de se\u00f1alizaci\u00f3n implicadas"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Yolanda Ruiz Le\u00f3n <\/strong><\/h2>\n<p>La prote\u00edna beta-amiloide es el componente mayoritario de las placas seniles que se observan en la enfermedad de alzheimer. Se genera por procesamiento a partir de la prote\u00edna precursora del p\u00e9ptido beta-amiloide (app), una proteina de membrana cuya sobreexpresi\u00f3n est\u00e1 directamente relacionada con el desarrollo de la enfermedad. El \u00e1cido retinoico (ar) induce la expresi\u00f3n de app en c\u00e9lulas de neuroblastoma. Sin embargo, el efecto requiere tiempos largos de tratamiento, y adem\u00e1s el promotor de app no contiene ning\u00fan elemento consenso de uni\u00f3n a los receptores de ar (rare), lo que parece descartar un efecto directo de este ligando a nivel transcripcional. En esta tesis, hemos demostrado que el ar puede regular la expresi\u00f3n de app a trav\u00e9s de sus efectos previos sobre el mrna del receptor trkb. Bdnf es capaz de estimular la actividad del promotor de app en  c\u00e9lulas de neuroblastoma humano sh-sy5y, y el tratamiento con ar permitir\u00eda este est\u00edmulo induciendo la s\u00edntesis de su receptor trkb. La activaci\u00f3n transcripcional del promotor de app por bdnf es dependiente de la actividad tirosina quinasa de trkb y se lleva a cabo principalmente a trav\u00e9s del sitio shc del receptor. La regulaci\u00f3n de app por bdnf, que es independiente de la actividad plc-y\/pkc, estar\u00eda mediada principalmente a trav\u00e9s de otras dos v\u00eda de se\u00f1alizaci\u00f3n, la v\u00eda ras\/mapk y la v\u00eda p13k\/akt, que presentan varios puntos de inteferencia entre s\u00ed. En este sentido, nuestros resultados sugieren un posible efecto permisivo y\/o activador de raf y mek sobre la v\u00eda p13k\/akt. A otro nivel,hemos estudiado las secuencias del promotor de app que median la respuesta a bdnf. Mediante deleciones sucesivas hemos probado que la respuesta a bdnf est\u00e1 mediada fundamentalmente a trav\u00e9s de secuencias localizadas entre los nucle\u00f3ticos -307 a -15. M\u00e1s a\u00fan, nuestros resultados han demostrado que el efecto delbdnf es independiente de los sitios ap-1 presentes en esta regi<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Regulaci\u00f3n del gen de la proteina precursora del peptido beta-amilode por acido retinoico y bdnf; mecanismos de accion y vias de se\u00f1alizaci\u00f3n implicadas<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Regulaci\u00f3n del gen de la proteina precursora del peptido beta-amilode por acido retinoico y bdnf; mecanismos de accion y vias de se\u00f1alizaci\u00f3n implicadas <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Yolanda Ruiz Le\u00f3n <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 20\/07\/2001<\/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>Angel Pascual Garc\u00eda<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: javier Le\u00f3n serrano <\/li>\n<li>Mar\u00eda  del pilar Perez gonzalez (vocal)<\/li>\n<li>Luis Miguel Garc\u00eda segura (vocal)<\/li>\n<li>Francisco Wandosell jurado (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Yolanda Ruiz Le\u00f3n La prote\u00edna beta-amiloide es el componente mayoritario de las placas seniles que se observan [&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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