{"id":102507,"date":"2022-12-14T13:22:05","date_gmt":"2022-12-14T12:22:05","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=102507"},"modified":"2022-12-15T13:21:44","modified_gmt":"2022-12-15T12:21:44","slug":"a-new-atlas-unveils-which-mutations-are-behind-the-noxious-amyloid-formation","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/un-nou-atles-revela-quines-mutacions-estan-darrere-de-la-formacio-nociva-d-amiloide_\/","title":{"rendered":"Un nou atles revela quines mutacions estan darrere de la formaci\u00f3 nociva d’amiloide\u00a0"},"content":{"rendered":"\n

Investigadors de l’Institut de Bioenginyeria de Catalunya (IBEC) han elaborat l’atles m\u00e9s complet fins avui amb les mutacions gen\u00e8tiques que causen la formaci\u00f3 de fibril\u00b7les d’amiloide BETA, una prote\u00efna que est\u00e0 darrere de la malaltia d’Alzheimer. L’estudi, liderat per la investigadora de l’IBEC, Benedetta Bolognesi, en col\u00b7laboraci\u00f3 amb el grup de Bel Lehner en el Centre de Regulaci\u00f3 Gen\u00f2mica (CRG), ha estat publicat en la prestigiosa revista cient\u00edfica Nature Communications<\/em>.<\/h4>\n\n\n\n
\"\"<\/figure>\n\n\n\n

Les fibril\u00b7les amiloide s\u00f3n agregats de prote\u00efnes que s’acumulen al voltant de les c\u00e8l\u00b7lules, sense que l’organisme aconsegueixi descompondre-les. La seva pres\u00e8ncia i proc\u00e9s de formaci\u00f3 semblen ser la causa de m\u00e9s de 50 malalties humanes, incloses la malaltia d’Alzheimer, la malaltia de Parkinson, la dem\u00e8ncia frontotemporal, l’esclerosi lateral amiotr\u00f2fica (ELA) i la diabetis tipus II.<\/p>\n\n\n\n

Els investigadors ja han aconseguit descobrir l’estructura de moltes fibril\u00b7les d’amiloide. No obstant aix\u00f2, el mecanisme pel qual es formen, conegut com a reacci\u00f3 de nucleaci\u00f3, continua sent un misteri. Entendre aquest mecanisme \u00e9s fonamental si es volen prevenir algunes de les principals patologies que afecten la nostra societat.<\/p>\n\n\n\n

Amb l’escaneig mutacional profund, una t\u00e8cnica d’an\u00e0lisi cel\u00b7lular d’alt rendiment, s’aconsegueixen caracteritzar milers de mutacions gen\u00e8tiques que condueixen a l’agregaci\u00f3 de la prote\u00efna amiloide. Fins ara les t\u00e8cniques d’exploraci\u00f3 de mutacions profundes tendeixen a observar nom\u00e9s substitucions (mutacions en les quals un bloc de construcci\u00f3 d’ADN reempla\u00e7a a un altre), i ignorar, en gran manera, altres tipus com les insercions (mutacions on s’afegeix un bloc de construcci\u00f3) o les delecions (mutacions en les quals s’elimina un bloc de construcci\u00f3) a pesar de que tots dos mecanismes poden ser determinants per a l’acumulaci\u00f3 d’amiloide.<\/p>\n\n\n\n

Mireia Seuma, investigadora del grup de Benedetta Bolognesi en l’IBEC, ha aconseguit desenvolupar un atles complet que compara els m\u00faltiples tipus de mutacions i avalua el seu paper en la formaci\u00f3 de fibril\u00b7les d’amiloide. El seu treball es va publicar recentment en la prestigiosa revista cient\u00edfica Nature Communications<\/em>.<\/p>\n\n\n\n

Mutacions que emmalalteixen<\/strong><\/strong><\/p>\n\n\n\n

L’estudi en q\u00fcesti\u00f3 va analitzar un p\u00e8ptid de 42 amino\u00e0cids, on es van identificar 307 mutacions que acceleren l’acumulaci\u00f3 d’amiloide, un 10% del total de les mutacions detectades, entre les quals es trobaven moltes que no corresponien a substitucions, sin\u00f3 a alteracions del tipus inserci\u00f3 i deleci\u00f3. D’altra banda, l’elevat nombre de mutacions identificades en aquest p\u00e8ptid tan curt posa de manifest l’enorme diversitat de variacions que es poden donar en el genoma hum\u00e0. Aquestes mutacions poden resultar o no en malaltia, ressaltant la necessitat de saber quin impacte tenen en la nucleaci\u00f3 d’amiloide.
<\/p>\n\n\n\n

A m\u00e9s, els investigadors van observar que el 87% de les mutacions amb probabilitat de ser patog\u00e8niques es troben en un extrem espec\u00edfic del p\u00e8ptid, conegut com a N-terminal. Els truncaments en aquesta regi\u00f3 van resultar ser especialment eficaces accelerant la nucleaci\u00f3 i es preveu, per tant, que aquesta regi\u00f3 jugui un gran paper en el desenvolupament de l\u2019Alzheimer.<\/p>\n\n\n\n

En el seu conjunt, aquest treball proporciona una guia integral per a la interpretaci\u00f3 cl\u00ednica futura de les mutacions i resulta en una eina molt \u00fatil per a aquells investigadors que realitzen recerques b\u00e0siques i cl\u00edniques sobre tots els trastorns que s’amaguen darrere dels agregats d’amiloide.<\/p>\n\n\n\n

Reference article:<\/strong> Seuma, M., Lehner, B. & Bolognesi, B. An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation<\/a>. Nat Commun<\/em> 13, 7084 (2022). https:\/\/doi.org\/10.1038\/s41467-022-34742-3<\/p>\n\n\n\n

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

Investigadors de l’Institut de Bioenginyeria de Catalunya (IBEC) han elaborat l’atles m\u00e9s complet fins avui amb les mutacions gen\u00e8tiques que causen la formaci\u00f3 de fibril\u00b7les d’amiloide BETA, una prote\u00efna que est\u00e0 darrere de la … Read more<\/a><\/p>\n","protected":false},"author":4,"featured_media":102501,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[1627,1107,1871,1776],"post_formats":[],"class_list":["post-102507","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-alzheimer-ca-2","tag-benedetta-bolognesi-ca","tag-mutacions-genetiques","tag-protein-phase-transitions-in-health-and-disease-ca"],"yoast_head":"\nUn nou atles revela quines mutacions estan darrere de la formaci\u00f3 nociva d'amiloide\u00a0 - 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\/un-nou-atles-revela-quines-mutacions-estan-darrere-de-la-formacio-nociva-d-amiloide_\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Un nou atles revela quines mutacions estan darrere de la formaci\u00f3 nociva d'amiloide\u00a0 - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadors de l’Institut de Bioenginyeria de Catalunya (IBEC) han elaborat l’atles m\u00e9s complet fins avui amb les mutacions gen\u00e8tiques que causen la formaci\u00f3 de fibril\u00b7les d’amiloide BETA, una prote\u00efna que est\u00e0 darrere de la ... 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