{"id":105453,"date":"2010-03-12T00:00:00","date_gmt":"2010-03-12T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-de-las-funciones-fisiologicas-y-patologicas-de-la-protea%c2%adna-tau-mediante-el-uso-de-modelos-murinos-deficientes-en-tau\/"},"modified":"2010-03-12T00:00:00","modified_gmt":"2010-03-12T00:00:00","slug":"estudio-de-las-funciones-fisiologicas-y-patologicas-de-la-protea%c2%adna-tau-mediante-el-uso-de-modelos-murinos-deficientes-en-tau","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-celular\/estudio-de-las-funciones-fisiologicas-y-patologicas-de-la-protea%c2%adna-tau-mediante-el-uso-de-modelos-murinos-deficientes-en-tau\/","title":{"rendered":"Estudio de las funciones fisiol\u00f3gicas y patol\u00f3gicas de la prote\u00edna tau mediante el uso de modelos murinos deficientes en tau"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Elena Gomez De Barreda Santiago <\/strong><\/h2>\n<p>Tau is a major neuronal microtubule-associated protein whose main known biological function is to stimulate microtubule assembly and to stabilize the microtubule network that composes the axon. Tau protein has been primarily studied due to its dysfunction in a subset of neurodegenerative disorders known as tauopathies, the most common of which is alzheimer\u00c2\u00bfs disease. These pathologies are characterized by the accumulation of abnormally hyperphosphorylated tau aggregates in the central nervous system, distributed in a pattern which correlates with the progression of dementia. It remains unclear whether the deleterious effects of tau pathologies result from a toxic gain-of-function by hyperphosphorylated and\/or aggregated tau or from critical losses of normal tau function in the disease state. in order to elucidate this controversial issue, we took advantage of a transgenic mouse model in which the tau gene is disrupted. We observed that tau deficiency affected hdac6-mediated tubulin acetylation, leading to decreased acetylated-tubulin levels. In fact, we demonstrate an interaction between tau and hdac6 which we propose results in hdac6 inhibition. To further investigate tau functions, we performed a genetic array to analyze tau deficiency-derived gene expression alterations. The transcriptional analysis revealed that tau deficiency led to upregulation of the smarce1 gene, which encodes baf57 protein. Baf57 is involved in the repression of neuron specific genes, which may explain the observed delay in axonal elongation in tau deficient neurons. We also demonstrated decreased calbindin and calmodulin levels in tau deficient mice, which may correlate with reduced calcium-buffering capacity in the absence of tau. to determine the toxic role of hyperphosphorylated tau, we generated a transgenic mouse model lacking tau protein and overexpressing gsk3\u00edY. These mice showed a delay in the progression of neurodegeneration, suggesting that tau phosphorylation results in a toxic gain-of function.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio de las funciones fisiol\u00f3gicas y patol\u00f3gicas de la prote\u00edna tau mediante el uso de modelos murinos deficientes en tau<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio de las funciones fisiol\u00f3gicas y patol\u00f3gicas de la prote\u00edna tau mediante el uso de modelos murinos deficientes en tau <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Elena Gomez De Barreda Santiago <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 03\/12\/2010<\/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>Jes\u00fas Avila De Grado<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: pilar Gomez ramos <\/li>\n<li>Marta Nieto l\u00f3pez (vocal)<\/li>\n<li>Miguel D\u00edaz hern\u00e1ndez (vocal)<\/li>\n<li>Ana Mar\u00eda Mata dur\u00e1n (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Elena Gomez De Barreda Santiago Tau is a major neuronal microtubule-associated protein whose main known biological function [&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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