{"id":97105,"date":"2009-09-11T00:00:00","date_gmt":"2009-09-11T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/discovery-and-development-of-apaf-1-inhibitors-advancing-towards-unwanted-cell-death-treatments\/"},"modified":"2009-09-11T00:00:00","modified_gmt":"2009-09-11T00:00:00","slug":"discovery-and-development-of-apaf-1-inhibitors-advancing-towards-unwanted-cell-death-treatments","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-celular\/discovery-and-development-of-apaf-1-inhibitors-advancing-towards-unwanted-cell-death-treatments\/","title":{"rendered":"Discovery and development of apaf-1 inhibitors: advancing towards unwanted cell death treatments"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Laura Mondrag\u00f3n Mart\u00ednez <\/strong><\/h2>\n<p>La apoptosis es un proceso a trav\u00e9s del cu\u00e1l la c\u00e9lula sufre una serie de cambios morfol\u00f3gicos que llevan a su autodestrucci\u00f3n de una manera ordenada y silenciosa. La apoptosis juega un papel clave en la homeostasis de los tejidos, en el desarrollo embrionario, el desarrollo del sistema immune. Asimismo, es la principal causa de muerte en los tejidos que rodean a lesiones agudas como la isquemia. Como consecuencia, cualquier defecto en la apoptosis est\u00e1 asociado a la aparici\u00f3n de una serie de patolog\u00edas. As\u00ed, la ausencia de apoptosis est\u00e1 relacionada con la aparici\u00f3n del c\u00e1ncer, mientras que una apoptosis excesiva es la causante de da\u00f1os tisulares despu\u00e9s de procesos de hipoxia, aparici\u00f3n de enfermedades neurodegenerativas entre otros.  una prote\u00edna clave en la inducci\u00f3n de la apoptosis es apaf-1. En nuestro laboratorio se eligi\u00f3 esta prote\u00edna como diana en el desarrollo de f\u00e1rmacos que pueden disminuir la apoptosis excesiva. En este proyecto de tesis se describe el desarrollo y s\u00edntesis de mol\u00e9culas inhibidoras de apaf-1 partiendo de una mol\u00e9cula previamente desarrollada en el laboratorio, el peptoide 1.  en esta tesis doctoral se describe el desarrollo de una segunda generaci\u00f3n de derivados del peptoide 1 no t\u00f3xicos y capaces de frenar los procesos de apoptosis en diferentes modelos celulares. Asimismo, se ha determinado el mecanismo de acci\u00f3n de estos compuestos. Son capaces de ejercer su funci\u00f3n inhibidora mediante la uni\u00f3n a la prote\u00edna apaf-1 y la inhibici\u00f3n de su capacidad para reclutar y activar a la proteasa procaspasa 9, frenando as\u00ed el proceso de apoptosis. Se determinaron tambi\u00e9n las consecuencias para la c\u00e9lula de la inhibici\u00f3n de la prote\u00edna apaf-1 tras un est\u00edmulo apopt\u00f3tico y se determin\u00f3 un marcado incremento de la viabilidad celular. Finalmente, la estrategia utilizada fue validada para su posible aplicaci\u00f3n en cl\u00ednica a trav\u00e9s del desarrollo de un modelo de isquemia en caliente en rata.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Discovery and development of apaf-1 inhibitors: advancing towards unwanted cell death treatments<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Discovery and development of apaf-1 inhibitors: advancing towards unwanted cell death treatments <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Laura Mondrag\u00f3n Mart\u00ednez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Universitat de val\u00e9ncia (estudi general)<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 09\/11\/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>Enrique Perez Paya<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: seamus Martin <\/li>\n<li>francesco Cecconi (vocal)<\/li>\n<li>cristina Mu\u00f1oz pinedo (vocal)<\/li>\n<li>ruth Duncan (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Laura Mondrag\u00f3n Mart\u00ednez La apoptosis es un proceso a trav\u00e9s del cu\u00e1l la c\u00e9lula sufre una serie [&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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