{"id":77075,"date":"2005-08-11T00:00:00","date_gmt":"2005-08-11T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/enfermedad-de-alzheimer-alpha-halometilcetonas-hmks-sintesis-y-estudio-de-nuevos-inhibidores-atp-no-competitivos-de-gsk-3beta\/"},"modified":"2005-08-11T00:00:00","modified_gmt":"2005-08-11T00:00:00","slug":"enfermedad-de-alzheimer-alpha-halometilcetonas-hmks-sintesis-y-estudio-de-nuevos-inhibidores-atp-no-competitivos-de-gsk-3beta","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/enfermedad-de-alzheimer-alpha-halometilcetonas-hmks-sintesis-y-estudio-de-nuevos-inhibidores-atp-no-competitivos-de-gsk-3beta\/","title":{"rendered":"Enfermedad de alzheimer alpha halometilcetonas (hmks). sintesis y estudio de nuevos inhibidores atp no competitivos de gsk 3beta"},"content":{"rendered":"<h2>Tesis doctoral de <strong>  Perez Fernandez Daniel Ignacio <\/strong><\/h2>\n<p>Las dos lesiones histopatol\u00f3gicas principales de la enfermedad de alzheimer son las placas seniles y los ovillos neurofibrilares. El componente principal de los ovillos neurofibrilares es la proteina tau hiperfosforilada. Dicha fosforilaci\u00f3n de la prote\u00edna quinasa est\u00e1 regulada principalmente por la glic\u00f3geno sintasa quinasa 3- beta (gsk-3beta)  una buena estrategia terap\u00e9utica para poder disminuir la fosforilacion de gsk-3beta y evitar la formaci\u00f3n de los ovillos neurofibrilares ser\u00eda mediante el empleo de inhibidores de dicha prote\u00edna.  a partir de un cabeza de serie obtenido de nuestra quimioteca de compuestos que inhibia a dicha prote\u00edna, se realizaron diversas modificaciones sint\u00e9ticas con el fin de obtener compuestos m\u00e1s potentes. Una vez sintetizados se llevaron a cabo diversos estudios tanto te\u00f3ricos, como experimentales.  en primer lugar los compuestos no competian con el atp por el sitio activo de la enzima, principal ventaja respecto al resto de inhibidores descritos en la bibliograf\u00eda.  se realiz\u00f3 un estudio comfa con el fin de obtener un modelo capaz de predecir la actividad biol\u00f3gica de nuevas estructuras.  los derivados sintetizados eran capaces de atravesar la membrana biol\u00f3gica tras realizar ensayos celulares en los que se observaba la disminuci\u00f3n de la fosforilaci\u00f3n de la prote\u00edna tau.  las halometilcetonas se mostraron selectivas frente a distintas prote\u00ednas quinasas presentes en el sistema nevioso central y se midi\u00f3 la uni\u00f3n a distintos receptores neuronales que intervienen  en la enfermedad de alzheimer.  mediante estudios te\u00f3ricos y experimentales se determin\u00f3 que los compuestos eran capaces de pasar la barrera hematoencef\u00e1lica y presentar una buena absorci\u00f3n oral.  por hplc se midi\u00f3 su grado de uni\u00f3n a distintas prote\u00ednas plasm\u00e1ticas observando que los compuestos no se un\u00edan a ellas con lo que se encontar\u00edan en una proporci\u00f3n elevada en el organismo.  por \u00faltimo uno de lo<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Enfermedad de alzheimer alpha halometilcetonas (hmks). sintesis y estudio de nuevos inhibidores atp no competitivos de gsk 3beta<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Enfermedad de alzheimer alpha halometilcetonas (hmks). sintesis y estudio de nuevos inhibidores atp no competitivos de gsk 3beta <\/li>\n<li><strong>Autor:<\/strong>\u00a0  Perez Fernandez Daniel Ignacio <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 08\/11\/2005<\/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>Santiago Conde Ruzafa<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal:  De mendoza sans fco. javier <\/li>\n<li>nadine Jagerovic (vocal)<\/li>\n<li>Ana Martinez gil (vocal)<\/li>\n<li>marina Gordaliza escobar (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Perez Fernandez Daniel Ignacio Las dos lesiones histopatol\u00f3gicas principales de la enfermedad de alzheimer son las placas [&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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