{"id":102508,"date":"2022-12-14T13:22:05","date_gmt":"2022-12-14T12:22:05","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=102508"},"modified":"2022-12-14T16:58:41","modified_gmt":"2022-12-14T15:58:41","slug":"a-new-atlas-unveils-which-mutations-are-behind-the-noxious-amyloid-formation","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/es\/un-nuevo-atlas-desvela-que-mutaciones-estan-detras-de-la-formacion-nociva-de-amiloide","title":{"rendered":"Un nuevo atlas desvela qu\u00e9 mutaciones est\u00e1n detr\u00e1s de la formaci\u00f3n nociva de amiloide"},"content":{"rendered":"\n<h4 class=\"wp-block-heading\">Investigadores del Instituto de Bioingenier\u00eda de Catalu\u00f1a (IBEC) han elaborado el atlas m\u00e1s completo hasta la fecha con las mutaciones gen\u00e9ticas que causan la formaci\u00f3n de fibrillas de amiloide BETA, una prote\u00edna que est\u00e1 detr\u00e1s de la enfermedad de Alzh\u00e9imer. El estudio, liderado por la investigadora del IBEC, Benedetta Bolognesi, en colaboraci\u00f3n con el grupo de Bel Lehner en el Centro de Regulaci\u00f3n Gen\u00f3mica (CRG), ha sido publicado en la prestigiosa revista cient\u00edfica <em>Nature Communications<\/em>.<\/h4>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" width=\"1024\" height=\"682\" data-src=\"https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2022\/12\/insertions_web-1024x682.jpg\" alt=\"\" class=\"wp-image-102500 lazyload\" data-srcset=\"https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2022\/12\/insertions_web-1024x682.jpg 1024w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2022\/12\/insertions_web-300x200.jpg 300w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2022\/12\/insertions_web-768x511.jpg 768w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2022\/12\/insertions_web-1200x800.jpg 1200w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2022\/12\/insertions_web-600x400.jpg 600w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2022\/12\/insertions_web.jpg 1329w\" data-sizes=\"(max-width: 1024px) 100vw, 1024px\" src=\"data:image\/svg+xml;base64,PHN2ZyB3aWR0aD0iMSIgaGVpZ2h0PSIxIiB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciPjwvc3ZnPg==\" style=\"--smush-placeholder-width: 1024px; --smush-placeholder-aspect-ratio: 1024\/682;\" \/><\/figure>\n\n\n\n<p>Las fibrillas de amiloide son agregados de prote\u00ednas que se acumulan alrededor de las c\u00e9lulas, sin que el organismo consiga descomponerlas. Su presencia y proceso de formaci\u00f3n parecen ser la causa de m\u00e1s de 50 enfermedades humanas, incluidas la enfermedad de Alzheimer, la enfermedad de Parkinson, la demencia frontotemporal, la esclerosis lateral amiotr\u00f3fica (ELA) y la diabetes tipo II.<\/p>\n\n\n\n<p>Los investigadores ya han conseguido descubrir la estructura de muchas fibrillas de amiloide. Sin embargo, el mecanismo por el cual se forman, conocido como reacci\u00f3n de nucleaci\u00f3n, sigue siendo un misterio. Entender este mecanismo es fundamental si se quieren prevenir algunas de las principales patolog\u00edas que afectan a nuestra sociedad.<\/p>\n\n\n\n<p>Con el escaneo mutacional profundo, una t\u00e9cnica de an\u00e1lisis celular de alto rendimiento, se consiguen caracterizar miles de mutaciones gen\u00e9ticas que conducen a la agregaci\u00f3n de la prote\u00edna amiloide. Hasta ahora las t\u00e9cnicas de exploraci\u00f3n de mutaciones profundas tienden a observar solo <em>sustituciones<\/em> (mutaciones en las que un bloque de construcci\u00f3n de ADN reemplaza a otro), e ignorar, en gran medida, otros tipos como las <em>inserciones<\/em> (mutaciones donde se a\u00f1ade un bloque de construcci\u00f3n) o las <em>deleciones<\/em> (mutaciones en las que se elimina un bloque de construcci\u00f3n) a pesar de que ambos mecanismos pueden ser determinantes para la acumulaci\u00f3n de amiloide.<\/p>\n\n\n\n<p>Mireia Seuma, investigadora del grupo de <a href=\"https:\/\/ibecbarcelona.eu\/es\/tag\/benedetta-bolognesi-es\/\">Benedetta Bolognesi<\/a> en el IBEC, ha logrado desarrollar un atlas completo que compara los m\u00faltiples tipos de mutaciones y eval\u00faa su papel en la formaci\u00f3n de fibrillas de amiloide. Su trabajo se public\u00f3 recientemente en la prestigiosa revista cient\u00edfica, <em>Nature Communications<\/em>.<\/p>\n\n\n\n<p><strong><strong>Mutaciones que enferman<\/strong><\/strong><\/p>\n\n\n\n<p>El estudio en cuesti\u00f3n analiz\u00f3 un p\u00e9ptido de 42 amino\u00e1cidos, donde se identificaron 307 mutaciones que aceleran la acumulaci\u00f3n de amiloide, un 10 % del total de las mutaciones detectadas, entre las que se encontraban muchas que no correspond\u00edan a <em>sustituciones<\/em>, sino a alteraciones del tipo <em>inserci\u00f3n<\/em> y <em>deleci\u00f3n<\/em>. Por otro lado, el elevado n\u00famero de mutaciones identificadas en este p\u00e9ptido tan corto pone de manifiesto la enorme diversidad de variaciones que se pueden dar en el genoma humano. Estas mutaciones pueden resultar o no en enfermedad, resaltando la necesidad de saber qu\u00e9 impacto tienen en la nucleaci\u00f3n de amiloide. &nbsp;<\/p>\n\n\n\n<p>Adem\u00e1s, los investigadores observaron que el 87 % de las mutaciones con probabilidad de ser patog\u00e9nicas se encuentran en un extremo espec\u00edfico del p\u00e9ptido, conocido como N-terminal. Los truncamientos en esta regi\u00f3n resultaron ser especialmente eficaces acelerando la nucleaci\u00f3n y se prev\u00e9, por tanto, que esta regi\u00f3n juegue un gran papel en el desarrollo del alzh\u00e9imer.<\/p>\n\n\n\n<p>En su conjunto, este trabajo proporciona una gu\u00eda integral para la interpretaci\u00f3n cl\u00ednica futura de las mutaciones y resulta en una herramienta muy \u00fatil para aquellos investigadores que realizan investigaciones b\u00e1sicas y cl\u00ednicas sobre todos los trastornos que se esconden detr\u00e1s de los agregados de amiloide.<\/p>\n\n\n\n<p><strong>Art\u00edculo referenciado:<\/strong> Seuma, M., Lehner, B. &amp; Bolognesi, B. <a rel=\"noreferrer noopener\" href=\"https:\/\/doi.org\/10.1038\/s41467-022-34742-3\" target=\"_blank\">An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation<\/a>.&nbsp;<em>Nat Commun<\/em>&nbsp;13, 7084 (2022). https:\/\/doi.org\/10.1038\/s41467-022-34742-3<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigadores del Instituto de Bioingenier\u00eda de Catalu\u00f1a (IBEC) han elaborado el atlas m\u00e1s completo hasta la fecha con las mutaciones gen\u00e9ticas que causan la formaci\u00f3n de fibrillas de amiloide BETA, &#8230; <a title=\"Un nuevo atlas desvela qu\u00e9 mutaciones est\u00e1n detr\u00e1s de la formaci\u00f3n nociva de amiloide\" class=\"read-more\" href=\"https:\/\/ibecbarcelona.eu\/es\/un-nuevo-atlas-desvela-que-mutaciones-estan-detras-de-la-formacion-nociva-de-amiloide\" aria-label=\"More on Un nuevo atlas desvela qu\u00e9 mutaciones est\u00e1n detr\u00e1s de la formaci\u00f3n nociva de amiloide\">Read more<\/a><\/p>\n","protected":false},"author":4,"featured_media":102502,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[97],"tags":[1628,1108,1870,1777],"post_formats":[],"class_list":["post-102508","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticias-de-investigacion","tag-alzheimer-es-2","tag-benedetta-bolognesi-es","tag-mutaciones-geneticas","tag-protein-phase-transitions-in-health-and-disease-es"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Un nuevo atlas desvela qu\u00e9 mutaciones est\u00e1n detr\u00e1s de la formaci\u00f3n nociva de amiloide - Institute for Bioengineering of Catalonia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibecbarcelona.eu\/es\/un-nuevo-atlas-desvela-que-mutaciones-estan-detras-de-la-formacion-nociva-de-amiloide\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Un nuevo atlas desvela qu\u00e9 mutaciones est\u00e1n detr\u00e1s de la formaci\u00f3n nociva de amiloide - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadores del Instituto de Bioingenier\u00eda de Catalu\u00f1a (IBEC) han elaborado el atlas m\u00e1s completo hasta la fecha con las mutaciones gen\u00e9ticas que causan la formaci\u00f3n de fibrillas de amiloide BETA, ... 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