{"id":80328,"date":"2020-11-28T09:04:36","date_gmt":"2020-11-28T08:04:36","guid":{"rendered":"http:\/\/ibecbarcelona.eu\/?p=80328"},"modified":"2020-12-11T12:23:07","modified_gmt":"2020-12-11T11:23:07","slug":"descobreixen-un-mecanisme-per-creuar-la-barrera-protectora-del-cervell","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/descobreixen-un-mecanisme-per-creuar-la-barrera-protectora-del-cervell\/","title":{"rendered":"Descobreixen un mecanisme per creuar la barrera protectora del cervell"},"content":{"rendered":"

\"\"<\/p>\n

El cervell \u00e9s l’\u00f2rgan m\u00e9s car del nostre cos en termes d’energia metab\u00f2lica; encara que nom\u00e9s pesa al voltant de<\/span>l 5% de la massa c<\/span>orporal, consumeix fins al 20% dels metab\u00f2lits i fins al 60% de la ingesta de sucre. No obstant aix\u00f2, el cervell \u00e9s impermeable al 95% dels f\u00e0rmacs coneguts, la qual cosa dificulta el desenvolupament de la majoria de ter\u00e0pies neurol\u00f2giques.<\/span>\u00a0<\/span><\/p>\n

Aquesta caracte<\/span>r\u00edstica exclusiva es deu a la capacitat d<\/span>el cervell per canviar la seva\u00a0<\/span>vasculatura<\/span>\u00a0i fer-lo m\u00e9s impermeable a la majoria de les mol\u00e8cules i m\u00e9s permeable als nutrients desitjats. La\u00a0<\/span>vasculatura<\/span>\u00a0cerebral es converteix efectivament en una barrera i, de fe<\/span>t, se la coneix com a barrera\u00a0<\/span>hematoencef\u00e0lica<\/span>\u00a0(BHE).<\/span>\u00a0<\/span><\/p>\n

No \u00e9s estrany, doncs, que els desequilibris que tenen lloc en aquesta barrera siguin tamb\u00e9 la base de moltes patologies relacionades amb el deteriorament cerebral i, per tant, estiguin implicades en mal<\/span>alties com l’Alzheimer. D’altra banda, aquesta estructura tamb\u00e9 \u00e9s la que impedeix que la majoria dels f\u00e0rmacs accedeixin al cervell, dificultant aix\u00ed el desenvolupament de tractaments espec\u00edfics per a malalties neuronals.<\/span>\u00a0<\/span><\/p>\n

Ara, un equip format per cient\u00edfi<\/span>cs de la Xina, els EUA, It\u00e0lia, Regne Unit i Espanya, liderat pel professor d’investigaci\u00f3 ICREA\u00a0<\/span>Giuseppe\u00a0<\/span>Battaglia<\/span><\/a>\u00a0del grup\u00a0<\/span>Molecular\u00a0<\/span>Bionics<\/span><\/a>\u00a0de l’<\/span>Institut de Bioenginyeria de Catalunya<\/span><\/a>\u00a0(IBEC) ha descrit com es\u00a0<\/span>d\u00f3na<\/span>\u00a0el transport de mol\u00e8cules a trav\u00e9s de les c\u00e8l\u00b7lules endotelials de cervell, ub<\/span>icades a la BHE. L’estudi, publicat a la prestigiosa revista\u00a0<\/span>Science<\/span>\u00a0<\/span>Advances<\/span><\/a>, mostra, a partir del model basat en la prote\u00efna 1 relacionada amb el receptor de lipoprote\u00efnes de baixa densitat (coneguda com LRP1) com l’avidesa de la c\u00e0rrega amb els receptor<\/span>s (\u00e9s a dir, com de fort est\u00e0 unida a ells) determina si les c\u00e8l\u00b7lules endotelials del cervell transporten la c\u00e0rrega a trav\u00e9s seu o, alternativament, la internalitzen en el seu propi metabolisme. En el primer cas, la c\u00e0rrega \u00e9s traslladada a trav\u00e9s de tra<\/span>nsportadors tubulars de curta durada que van i\u00a0<\/span>venen<\/span>\u00a0de el cervell a la sang, estabilitzats per la prote\u00efna “syndapin-2”. Aquesta prote\u00efna, coneguda per associar-se amb estructures tubulars, es converteix\u00a0<\/span>de facto<\/span><\/i>\u00a0en un marcador per mesurar el transport a\u00a0<\/span>trav\u00e9s de les c\u00e8l\u00b7lules endotelials i avaluar la salut de la BHE.<\/span>\u00a0<\/span><\/p>\n

Un “transbordador” per viatjar al cervell\u00a0<\/strong><\/h2>\n

En aquest estudi, per tal de dilucidar el tr\u00e0fic de LRP1\/Syndapin-2, els investigadors van utilitzar models\u00a0<\/span>in vitro<\/span><\/i>\u00a0i\u00a0<\/span>in\u00a0<\/span><\/i>vivo<\/span><\/i>\u00a0de BHE. En concret,\u00a0<\/span>van fer servir, en ratolins i rates<\/span>, construccions\u00a0<\/span>sint\u00e8tiques modificades amb lligands LRP1 de mida similar a la dels virus, anomenades\u00a0<\/span>polimerosom<\/span>e<\/span>s<\/span>, per avaluar com la\u00a0<\/span>multival\u00e8ncia<\/span>\u00a0(la capacitat dels objectes petits per unir-se entre si) i, per<\/span>\u00a0tant, el control de l’enlla\u00e7 mediat per LRP1 est\u00e0 darrere de les mol\u00e8cules que travessen la BHE.<\/span>\u00a0<\/span><\/p>\n

\"\"
Fig 1.<\/figcaption><\/figure>\n

Aix\u00ed doncs, aquest treball descriu per primera vegada el mecanisme pel qual el receptor LRP1 activa el transport vesicular o tubular. De fet, els estudis<\/span>\u00a0in\u00a0<\/span><\/i>v<\/span><\/i>ivo<\/span><\/i>\u00a0i<\/span>\u00a0in vitro<\/span><\/i>\u00a0mostren com l’avidesa entre la c\u00e0rrega a transportar i el receptor t\u00e9 un paper clau. En els casos en qu\u00e8 l’energia d’uni\u00f3 o l’avidesa \u00e9s alta, les c\u00e8l\u00b7lules inicien la formaci\u00f3 de ves\u00edcules. En aquest cas, la subst\u00e0ncia a transportar es meta<\/span>bolitza\u00a0<\/span>en el<\/span>\u00a0seu interior, degradant-<\/span>se\u00a0<\/span>dins d’aquestes cavitats i, possiblement, no arriba al seu dest\u00ed ja que \u00e9s consumida per la pr\u00f2pia c\u00e8l\u00b7lula endotelial. D’altra banda, davant d’una energia o avidesa mitjana, la prote\u00efna syndapin-2 inicia la creaci\u00f3 del<\/span>s<\/span>\u00a0“<\/span>passatges tubulars”, una entrada molt m\u00e9s eficient per arribar a<\/span>l cervell.<\/span>\u00a0<\/span><\/p>\n

Els resultats de l’estudi apunten a la for\u00e7a amb qu\u00e8 les subst\u00e0ncies s’uneixen a<\/span>l receptor LRP1 com a factor clau en la regulaci\u00f3 del transport a trav\u00e9s de la membrana\u00a0<\/span>hematoenc<\/span>ef\u00e0lica<\/span>.\u00a0<\/span>\u00a0<\/span><\/p>\n

\u00a0<\/em><\/strong><\/p>\n

\"\"<\/span><\/strong>Aquest treball obre noves vies per afrontar amb \u00e8xit un dels maj<\/span><\/span>ors reptes de la medicina moderna: trobar una entrada segura i efica\u00e7 per la qual fer arribar f\u00e0rmacs a el cervell.<\/span><\/span><\/strong><\/p>\n

Professor Giuseppe Battaglia<\/em><\/strong><\/p>\n

 <\/p><\/blockquote>\n

\u00a0<\/em><\/p>\n

Article de refer\u00e8ncia<\/span><\/span><\/strong>:<\/span><\/span>\u202f <\/span><\/span>Xiaohe<\/span><\/span>\u00a0<\/span><\/span>Tian<\/span><\/span>, Diana Moreira Leite,\u00a0<\/span><\/span>Edoardo<\/span><\/span>\u00a0<\/span><\/span>Scarpa<\/span><\/span>,\u00a0<\/span><\/span>Sophie<\/span><\/span>\u00a0<\/span><\/span>Nyberg<\/span><\/span>, Gavin\u00a0<\/span><\/span>Fullstone<\/span><\/span>, Joe Forth, Diana\u00a0<\/span><\/span>Lourenco<\/span><\/span>\u00a0<\/span><\/span>Matias<\/span><\/span>,\u00a0<\/span><\/span>Azzurra<\/span><\/span>\u00a0<\/span><\/span>Apriceno<\/span><\/span>, Alessandro Poma, Aroa Duro\u00a0<\/span><\/span>Castano<\/span><\/span>,\u00a0<\/span><\/span>Manish<\/span><\/span>\u00a0<\/span><\/span>Vuyyuru<\/span><\/span>, Lena\u00a0<\/span><\/span>Harker-Kirschneck<\/span><\/span>,\u00a0<\/span><\/span>Andela<\/span><\/span>\u00a0<\/span><\/span>Saric<\/span><\/span>,\u00a0<\/span><\/span>Zhongping<\/span><\/span>\u00a0<\/span><\/span>Zhang<\/span><\/span>, Pan\u00a0<\/span><\/span>Xiang<\/span><\/span>, Bin\u00a0<\/span><\/span>Fang,\u00a0<\/span><\/span>Yupeng<\/span><\/span>\u00a0<\/span><\/span>Tian<\/span><\/span>,\u00a0<\/span><\/span>Lei<\/span><\/span>\u00a0<\/span><\/span>Luo<\/span><\/span>,\u00a0<\/span><\/span>Loris<\/span><\/span>\u00a0<\/span><\/span>Rizzello<\/span><\/span>, Giuseppe\u00a0<\/span><\/span>Battaglia<\/span><\/span>.\u00a0<\/span><\/span>On\u00a0<\/span><\/span>t<\/span><\/span>he<\/span><\/span>\u00a0<\/span><\/span>shuttling<\/span><\/span>\u00a0<\/span><\/span>across<\/span><\/span>\u00a0<\/span><\/span>the<\/span><\/span>\u00a0<\/span><\/span>blood-brain<\/span><\/span>\u00a0<\/span><\/span>barrier<\/span><\/span>\u00a0via\u00a0<\/span><\/span>tubules<\/span><\/span>\u00a0<\/span><\/span>formation<\/span><\/span>:\u00a0<\/span><\/span>mechanism<\/span><\/span>\u00a0<\/span><\/span>and<\/span><\/span>\u00a0<\/span><\/span>cargo<\/span><\/span>\u00a0<\/span><\/span>avidity<\/span><\/span>\u00a0<\/span><\/span>bias<\/span><\/span><\/strong><\/em>.<\/span><\/span><\/a>\u00a0<\/span><\/span>Science<\/span><\/span>\u00a0<\/span><\/span>Advances<\/span><\/span>, 2020.<\/span><\/span>\u00a0<\/span><\/p>\n

 <\/p>\n

 <\/p>\n

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

Un estudi internacional dirigit per l’investigador de l’IBEC Giuseppe Battaglia ha identificat el mecanisme i les condicions que permeten que les mol\u00e8cules travessin de manera eficient la barrera hematoencef\u00e0lica, la capa protectora del cervell. Aquest estudi descriu el paper de la prote\u00efna LRP1, aclarint el cam\u00ed que permet l’entrada segura i eficient de f\u00e0rmacs al cervell. <\/h3>\n","protected":false},"author":4,"featured_media":80031,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[1330,1104],"post_formats":[],"class_list":["post-80328","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-barrera-hematoencefalica-ca","tag-giuseppe-battaglia-ca"],"yoast_head":"\nDescobreixen un mecanisme per creuar la barrera protectora del cervell - 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\/descobreixen-un-mecanisme-per-creuar-la-barrera-protectora-del-cervell\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Descobreixen un mecanisme per creuar la barrera protectora del cervell - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Un estudi internacional dirigit per l'investigador de l'IBEC Giuseppe Battaglia ha identificat el mecanisme i les condicions que permeten que les mol\u00e8cules travessin de manera eficient la barrera hematoencef\u00e0lica, la capa protectora del cervell. 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