{"id":82658,"date":"2021-03-09T09:03:43","date_gmt":"2021-03-09T08:03:43","guid":{"rendered":"http:\/\/ibecbarcelona.eu\/?p=82658"},"modified":"2021-03-18T10:33:45","modified_gmt":"2021-03-18T09:33:45","slug":"el-primer-mapa-complet-de-mutacions-de-plaques-amiloides-obre-noves-vies-per-a-la-deteccio-precoc-de-la-malaltia-dalzheimer","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/el-primer-mapa-complet-de-mutacions-de-plaques-amiloides-obre-noves-vies-per-a-la-deteccio-precoc-de-la-malaltia-dalzheimer\/","title":{"rendered":"El primer mapa complet de mutacions de plaques amiloides obre noves vies per a la detecci\u00f3 preco\u00e7 de la malaltia d’Alzheimer"},"content":{"rendered":"

\"\"<\/p>\n

Aquest primer mapa complet de mutacions t\u00e9 el potencial d’ajudar els genetistes cl\u00ednics a predir si les mutacions que es troben en la beta amiloide poden fer que un individu sigui m\u00e9s propens al desenvolupament de la malaltia d’Alzheimer. A m\u00e9s, tamb\u00e9 ajudar\u00e0 els investigadors a entendre millor els mecanismes biol\u00f2gics que controlen l’aparici\u00f3 de la malaltia.<\/p>\n

\u201cLa seq\u00fcenciaci\u00f3 gen\u00e8tica dels individus \u00e9s cada cop m\u00e9s com<\/span>\u00fa<\/span>. Com a resultat, estem trobant cada vegada m\u00e9s mutacions, per\u00f2 manquem els criteris per a predir el seu resultat. S\u00f3n <\/span>malignes<\/span> i requereixen intervenci\u00f3? O s\u00f3n neutrals o benignes?\u201d, <\/span>declara Benedetta Bolognesi<\/a>, una de les principals autores de l’estudi i l\u00edder junior de grup a l’Institut de<\/strong> Bioenginyeria de Catalunya, <\/strong>IBEC. <\/span><\/b>“Els <\/span>es<\/span>pecialistes poden utilitzar aquest mapa de manera proactiva per interpretar l’efecte d’una mutaci\u00f3<\/span>,<\/span> de manera que quan es troba en un individu<\/span>,<\/span> ja sabem que significa i<\/span> amb sort, que hem de fer<\/span>. S’han constru\u00eft mapes similars per al gen BRCA1 i el c\u00e0ncer de mama en el passat, i \u00e9s emocionant que puguem replicar aix\u00f2 per la malaltia d’Alzheimer.”<\/span>\u00a0<\/span><\/p>\n

Segons Ben Lehner, professor de recerca ICREA en el Centre de Regulaci\u00f3 Gen\u00f2mica (CRG) i coautor de l’estudi<\/strong>,<\/span><\/b> \u201caquest<\/span>a<\/span> \u00e9s la primera an\u00e0lisi a gran escala i el primer mapa complet de com les mutacions promouen i prevenen que una prote\u00efna formi fibril\u00b7les amiloides, donant-nos<\/span> una visi\u00f3 sense precedents d’aquest mecanisme, que tamb\u00e9 representa la principal diana terap\u00e8utica en la malaltia d’Alzheimer\u201d.<\/span>\u00a0<\/span>\"\"<\/span><\/b><\/p>\n

Imatge: <\/span>a l’esquerra, els efectes mitjana de les mutacions en beta amiloide visualitzats en talls transversals de variants de <\/span>fibril\u00b7les<\/span> amiloide. Taronja: les mutacions en aquesta posici\u00f3 disminueixen, en mitjana, l’agregaci\u00f3 amiloide. Blau: les mutacions en aquesta posici\u00f3 augmenten, en mitjana, l’agregaci\u00f3 amiloide. Al centre i a la dreta, les primeres i \u00faltimes autores de l’obra respectivament, Mireia <\/span>Seuma<\/span> i <\/span>Benedetta<\/span> Bolognesi<\/span>, totes dues de l’IBEC.<\/span>\u00a0<\/span><\/h6>\n

Les mutacions s\u00f3n el factor clau en l’aparici\u00f3 de la malaltia\u00a0<\/strong><\/h2>\n

La malaltia d’Alzheimer \u00e9s la forma m\u00e9s comuna de dem\u00e8ncia, una malaltia <\/span>neurodegenerativa<\/span> que afecta m\u00e9s de 50 milions de persones a tot el m\u00f3n. S’han realitzat molts assajos cl\u00ednics, per\u00f2 no existeix una prevenci\u00f3 o cura coneguda per a la malaltia. Els processos biol\u00f2gics que causen la malaltia d’Alzheimer estan associats amb el dip\u00f2sit d’agregats de prote\u00efnes, tamb\u00e9 <\/span>coneguts<\/span> com a plaques o fibril\u00b7les amiloides, en el cervell. Aquestes plaques es componen principalment del p\u00e8ptid beta amiloide (<\/span>A\u00df<\/span>) i la seva generaci\u00f3 \u00e9s t\u00f2xica per a les neurones. En condicions normals, els p\u00e8ptids beta amiloides s\u00f3n solubles, per\u00f2 en el context de la malaltia s’adhereixen entre si, agregant-se i formant grumolls de fibril\u00b7les llargues i insolubles, en un proc\u00e9s que una vegada iniciat <\/span>s’autoperpetua<\/span>.<\/span>\u00a0<\/span><\/p>\n

Estudis anteriors han demostrat que algunes formes rares heredit\u00e0ries i particularment agressives de la malaltia d’Alzheimer s\u00f3n causades per mutacions en el gen que codifica el p\u00e8ptid beta amiloide. <\/span>Ara, els investigadors de l’IBEC i CRG presenten el primer mapa complet de com les mutacions afecten la formaci\u00f3 de plaques de p\u00e8ptids beta amiloides i influeixen en l’aparici\u00f3 de la malaltia d’Alzheimer.\u00a0<\/strong><\/p>\n

Els investigadors van quantificar totes les possibles mutacions en el p\u00e8ptid beta amiloide i com influeixen en la formaci\u00f3 d’agregats mitjan\u00e7ant l’\u00fas d’un sistema d’alt rendiment basat en c\u00e8l\u00b7lules, <\/span>el creixement de les quals dep\u00e8n de<\/span> l’agregaci\u00f3 de les diferents versions de <\/span>A\u00df<\/span> en el seu interior. Aix\u00f2 els va permetre provar els efectes de m\u00e9s de 14.000 versions diferents de <\/span>A\u00df<\/span> en un sol experiment.<\/span>\u00a0<\/span><\/p>\n

Com a resultat, van observar que <\/span>el A\u00df42, la forma m\u00e9s abundant de p\u00e8ptid <\/span>A\u00df<\/span>, t\u00e9 una organitzaci\u00f3 modular; la taxa d’agregaci\u00f3 pot augmentar amb mutacions al comen\u00e7ament del p\u00e8ptid, mentre que disminueix quan ocorren mutacions a la regi\u00f3 final i hidr\u00f2foba del p\u00e8ptid. Els investigadors tamb\u00e9 van trobar que la c\u00e0rrega el\u00e8ctrica del p\u00e8ptid juga un paper important en la prevenci\u00f3 de l’agregaci\u00f3.<\/span>\u00a0<\/span><\/p>\n

Una t\u00e8cnica robusta que es pot aplicar a altres malalties\u00a0<\/strong><\/h2>\n

Els investigadors tamb\u00e9 van analitzar les catorze mutacions conegudes en el p\u00e8ptid <\/span>A\u00df<\/span> que causen la malaltia d’Alzheimer familiar, una forma heredit\u00e0ria de la malaltia. Van trobar que les catorze mutacions augmenten l’agregaci\u00f3 del p\u00e8ptid <\/span>A\u00df<\/span>. Segons els autors, aquest<\/span>a<\/span> \u00e9s una troballa molt important que suggereix que el mecanisme bioqu\u00edmic observat en aquest treball \u00e9s molt similar, i <\/span>possiblement<\/span> el mateix, al <\/span>que <\/span>causa la malaltia humana.<\/span>\u00a0<\/span><\/p>\n

“Aquestes mutacions s\u00f3n extremadament rares i es relacionen amb un nombre relativament petit de casos de malaltia d’Alzheimer. No obstant aix\u00f2, algunes ocorreran sens dubte en algun individu actualment viu en el planeta i, per tant, hem de poder predir les que s\u00f3n nocives i que causaran la malaltia. Aix\u00f2 pot ajudar-nos a identificar de manera pr<\/span>eco\u00e7<\/span>, si una persona t\u00e9 probabilitats de desenvolupar la malaltia per a aix\u00ed prendre mesures preventives quan sigui possible\u201d, conclou <\/span>Benedetta<\/span> Bolognesi<\/span>.<\/span>\u00a0<\/span><\/p>\n

Aquestes catorze mutacions conegudes s\u00f3n menys del 4% de totes les mutacions que poden oc\u00f3rrer en <\/span>A\u00df<\/span>. Aquest nou treball mesura els efectes de totes les m\u00e9s de 350 mutacions addicionals en <\/span>A\u00df<\/span>, identificant aquelles que acceleren la formaci\u00f3 d’agregats i, per tant, les mutacions que tenen m\u00e9s probabilitats de causar la malaltia d’Alzheimer.<\/span>\u00a0<\/span><\/p>\n

Ara estem desitjant construir mapes per a altres prote\u00efnes que causen diferents malalties neurodegeneratives com la malaltia de Parkinson i veure que les dades del nostre atles s’utilitzen en la cl\u00ednica.\u00a0<\/strong><\/p>\n

Mireia Seuma, primera autora del treball i investigadora de l’IBEC.\u00a0<\/strong><\/p>\n<\/blockquote>\n

\u00a0<\/span>Aquest projecte \u00e9s un estudi pilot per a una important col\u00b7laboraci\u00f3 internacional anomenada \u201c<\/span>Atles of Variant Effects<\/strong>\u201d (<\/span>https:\/\/www.varianteffect.org\/<\/span><\/a>) que t\u00e9 com a objectiu caracteritzar els efectes de cada possible mutaci\u00f3 en el genoma hum\u00e0 i identificar i comprendre totes les mutacions que provoquen milers de malalties diferents.<\/span>\u00a0<\/span><\/p>\n

\n
\n
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Article de refer\u00e8ncia<\/span><\/b>: <\/span><\/b>Mireia <\/span>Seuma<\/span>, Andre<\/span> J.<\/span> Faure<\/span>, Marta Badia, Ben <\/span>Lehner<\/span>, <\/span>Benedetta<\/span> Bolognesi<\/span>. <\/span>\u201c<\/span>The<\/span> genetic<\/span> landscape<\/span> for <\/span>amyloid<\/span> beta <\/span>fibril<\/span> nucleation<\/span> accurately<\/span> discriminates<\/span> familial<\/span> Alzheimer\u2019s<\/span> disease<\/span> mutations<\/span><\/a>.<\/span>\u201d <\/span>eLife<\/span> 2021; 10:e63364.<\/span>\u00a0<\/span><\/p>\n

\u00a0<\/span><\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Un estudi publicat a la revista eLife analitza totes les mutacions possibles en el p\u00e8ptid beta amiloide i determina com influeixen en la seva agregaci\u00f3 en plaques, un distintiu patol\u00f2gic de la malaltia d’Alzheimer. Tamb\u00e9 ajudar\u00e0 els investigadors a entendre millor els mecanismes biol\u00f2gics que controlen l’aparici\u00f3 de la malaltia.<\/h3>\n","protected":false},"author":4,"featured_media":82700,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[1455,1107,1454],"post_formats":[],"class_list":["post-82658","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-alzheimer-ca","tag-benedetta-bolognesi-ca","tag-mutacions"],"yoast_head":"\nEl primer mapa complet de mutacions de plaques amiloides obre noves vies per a la detecci\u00f3 preco\u00e7 de la malaltia d'Alzheimer - 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\/ca\/el-primer-mapa-complet-de-mutacions-de-plaques-amiloides-obre-noves-vies-per-a-la-deteccio-precoc-de-la-malaltia-dalzheimer\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"El primer mapa complet de mutacions de plaques amiloides obre noves vies per a la detecci\u00f3 preco\u00e7 de la malaltia d'Alzheimer - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Un estudi publicat a la revista eLife analitza totes les mutacions possibles en el p\u00e8ptid beta amiloide i determina com influeixen en la seva agregaci\u00f3 en plaques, un distintiu patol\u00f2gic de la malaltia d'Alzheimer. 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