{"id":95847,"date":"2009-10-09T00:00:00","date_gmt":"2009-10-09T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/ciclo-celular-y-neurodegeneracion-implicacion-de-la-e3-ubiquitina-ligasa-apc-c-cdh1-en-la-excitotoxicidad\/"},"modified":"2009-10-09T00:00:00","modified_gmt":"2009-10-09T00:00:00","slug":"ciclo-celular-y-neurodegeneracion-implicacion-de-la-e3-ubiquitina-ligasa-apc-c-cdh1-en-la-excitotoxicidad","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica\/ciclo-celular-y-neurodegeneracion-implicacion-de-la-e3-ubiquitina-ligasa-apc-c-cdh1-en-la-excitotoxicidad\/","title":{"rendered":"Ciclo celular y neurodegeneraci\u00f3n: implicaci\u00f3n de la e3 ubiquitina ligasa apc\/c-cdh1 en la excitotoxicidad"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Carolina Maestre Ferrin <\/strong><\/h2>\n<p>Los resultados presentados en esta tesis proponen, por primera vez, un mecanismo espec\u00edfico de excitotoxicidad, o muerte neuronal asociada a la estimulaci\u00f3n de receptores de glutamato, en el que participan prote\u00ednas implicadas en la regulaci\u00f3n del ciclo celular. Aqu\u00ed describimos que la estimulaci\u00f3n de los receptores de glutamato tipo nmda induce cambios en las neuronas compatibles con un intento de entrada en el ciclo celular. Sin embargo, dicho ciclo no parece completarse, ya que se precipita una muerte neuronal prematura. Aqu\u00ed hemos descifrado gran parte del mecanismo responsable de esta excitotoxicidad. As\u00ed, la activaci\u00f3n de calpa\u00edna por ca2+ que sigue a la estimulaci\u00f3n de receptores nmda promueve la proteolisis de p35 y la formaci\u00f3n del complejo activo cdk5\/p25, el cual hiper-fosforila cdh1, al menos, en los residuos ser-40, thr-121 y ser-163 causando su acumulaci\u00f3n en el citosol y, en consecuencia  la inactivaci\u00f3n de su e3 ubiquitina ligasa apc\/c. La triple fosforilaci\u00f3n de cdh1 por cdk5-p25 es necesaria y suficiente para inactivar apc\/c e inducir la acumulaci\u00f3n de su sustrato natural, ciclina b1, y apoptosis neuronal tras la activaci\u00f3n de los receptores nmda. Este mecanismo puede ayudar a identificar nuevas dianas moleculares para prevenir la muerte neuronal asociada a diversas enfermedades neurol\u00f3gicas, ya que una gran mayor\u00eda de \u00e9stas est\u00e1n asociadas a la estimulaci\u00f3n de los receptores de glutamato tipo nmda.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Ciclo celular y neurodegeneraci\u00f3n: implicaci\u00f3n de la e3 ubiquitina ligasa apc\/c-cdh1 en la excitotoxicidad<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Ciclo celular y neurodegeneraci\u00f3n: implicaci\u00f3n de la e3 ubiquitina ligasa apc\/c-cdh1 en la excitotoxicidad <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Carolina Maestre Ferrin <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Salamanca<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 10\/09\/2009<\/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>Juan  Pedro Bola\u00f1os Hernandez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Mar\u00eda \u00e1ngeles Moro s\u00e1nchez <\/li>\n<li>Mar\u00eda Sacrist\u00e1n mart\u00edn (vocal)<\/li>\n<li>Carlos Villalobos Jorge (vocal)<\/li>\n<li>david Santamar\u00eda velilla (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Carolina Maestre Ferrin Los resultados presentados en esta tesis proponen, por primera vez, un mecanismo espec\u00edfico 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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