Alguns defectes en la xarxa de vasos sanguinis del sistema nervi\u00f3s central s\u2019han associat a s\u00edmptomes inicials de malalties neurodegeneratives com la malaltia d\u2019Alzheimer i l\u2019esclerosi lateral amiotr\u00f2fica (ELA). Aquesta xarxa vascular tan complexa \u00e9s la que aporta els nutrients necessaris \u2014sobretot, glucosa i oxigen\u2014 per activar totes les funcions neuronals. Ara, un estudi liderat per l\u2019Institut d\u2019Investigaci\u00f3 Biom\u00e8tica de Bellvitge (IDIBELL) i la Universitat de Barcelona (UB) revela que la prote\u00efna TDP-43 \u00e9s essencial per formar una xarxa de vasos sanguinis estable i madura en el sistema nervi\u00f3s central.<\/p>\n
Segons el treball, destacat ara a la portada de la revista JCI Insight<\/em><\/a>, la prote\u00efna TDP-43 tamb\u00e9 \u00e9s determinant per mantenir la integritat de la barrera hematoencef\u00e0lica, que evita l\u2019arribada de t\u00f2xics i pat\u00f2gens al sistema nervi\u00f3s central. \u00c9s dirigit pel professor Eloi Monta\u00f1ez, investigador principal del grup de Malalties Sist\u00e8miques, Vasculars i Envelliment<\/a> de l’IDIBELL i de la UB, i hi participen equips de la Facultat de Biologia i l\u2019Institut de Biomedicina (IBUB) de la UB, l\u2019Institut de Recerca contra la Leuc\u00e8mia Josep Carreras i el Centre Nacional d\u2019An\u00e0lisi Gen\u00f2mica (CNAG-CRG).<\/p>\n <\/p>\n Quin \u00e9s el paper de la prote\u00efna TDP-43 en el sistema vascular? <\/strong><\/p>\n La prote\u00efna TDP-43 \u00e9s un factor clau per al funcionament del sistema nervi\u00f3s i la plasticitat neuronal. \u00c9s una prote\u00efna d\u2019uni\u00f3 a l\u2019ADN i l\u2019ARN que regula l\u2019expressi\u00f3 g\u00e8nica, i la seva disfunci\u00f3 s\u2019ha associat a diversos trastorns neurodegeneratius.<\/p>\n Tot i que en els darrers anys s\u2019ha avan\u00e7at molt en la comprensi\u00f3 de les funcions de TDP-43 en les neurones, encara no es coneixia b\u00e9 el paper que fan en les c\u00e8l\u00b7lules endotelials que integren el sistema circulatori, la formaci\u00f3 de nous vasos sanguinis (angiog\u00e8nesi) i la funci\u00f3 vascular.<\/p>\n \u00abEl treball desvela per primer cop que la TDP-43 \u00e9s essencial per a la formaci\u00f3 i l\u2019estabilitat dels vasos sanguinis del sistema nervi\u00f3s central, i per a la integritat de la barrera hematoencef\u00e0lica\u00bb, detalla el professor Eloi Monta\u00f1ez, del Departament de Ci\u00e8ncies Fisiol\u00f2giques de la UB.<\/p>\n La vascularitzaci\u00f3 del sistema nervi\u00f3s central i la formaci\u00f3 de la barrera hematoencef\u00e0lica estan regulades per diferents vies de senyalitzaci\u00f3; per exemple, la via de senyalitzaci\u00f3 a trav\u00e9s de les integrines que regula la interacci\u00f3 de les c\u00e8l\u00b7lules amb la matriu extracel\u00b7lular i la senyalitzaci\u00f3 duta a terme pel factor de transcripci\u00f3 \u03b2-catenina.<\/p>\n \u00abEn l\u2019estudi, hem descobert que la defici\u00e8ncia de la prote\u00efna TDP-43 altera la matriu extracel\u00b7lular que envolta els vasos sanguinis i redueix la senyalitzaci\u00f3 de la \u03b2-catenina en les c\u00e8l\u00b7lules endotelials\u00bb, apunta l\u2019investigador. \u00abAix\u00ed, els ratolins sense prote\u00efna TDP-43 endotelial presenten m\u00faltiples hemorr\u00e0gies i degeneraci\u00f3 vascular al cervell i la medul\u00b7la espinal\u00bb.<\/p>\n <\/p>\n Defectes vasculars i resposta inflamat\u00f2ria en neuroci\u00e8ncies <\/strong><\/p>\n Els autors tamb\u00e9 identifiquen la TDP-43 de les c\u00e8l\u00b7lules endotelials com un factor potencial que contribueix als defectes vasculars que desencadenen la resposta inflamat\u00f2ria observada en pacients diagnosticats amb malalties associades a la TDP-43.<\/p>\n \u00abAlgunes alteracions en els vasos sanguinis del sistema nervi\u00f3s central \u2014defectes en la integritat de la barrera hematoencef\u00e0lica o degeneraci\u00f3 de c\u00e8l\u00b7lules endotelials\u2014 s\u2019associen a les respostes inflamat\u00f2ries i immunit\u00e0ries que poden causar p\u00e8rdua neuronal. Aquest proc\u00e9s de degeneraci\u00f3 neuronal \u00e9s subjacent a l\u2019origen o la progressi\u00f3 de diversos trastorns neurol\u00f2gics \u2014ictus, retinopatia diab\u00e8tica\u2014 i algunes malalties neurodegeneratives com la malaltia d\u2019Alzheimer, l\u2019ELA i la LATE (en angl\u00e8s, limbic-predominant age-related TDP-43 encephalopathy<\/em>)\u00bb.<\/p>\n El nou treball ajudar\u00e0 a con\u00e8ixer millor els mecanismes moleculars que relacionen els defectes vasculars i la neuroinflamaci\u00f3. \u00abEl nostre objectiu ara \u00e9s analitzar si els defectes en la funci\u00f3 de la prote\u00efna TDP-43 a l\u2019endoteli dels vasos madurs podrien estar implicats en l\u2019ELA o en altres patologies associades a TDP-43, a causa de l\u2019augment de la permeabilitat vascular o b\u00e9 els processos d\u2019inflamaci\u00f3\u00bb, clou l\u2019investigador.<\/p>\n <\/p>\n <\/p>\n <\/p>\n L\u2019Institut d’Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) \u00e9s un centre de recerca en biomedicina creat l\u2019any 2004. Est\u00e0 participat per l’Hospital Universitari de Bellvitge i l\u2019Hospital de Viladecans de l’Institut Catal\u00e0 de la Salut, l’Institut Catal\u00e0 d’Oncologia, la Universitat de Barcelona i l\u2019Ajuntament de l\u2019Hospitalet de Llobregat.<\/em><\/p>\n L\u2019IDIBELL \u00e9s membre del Campus d’Excel\u00b7l\u00e8ncia Internacional de la Universitat de Barcelona HUBc i forma part de la instituci\u00f3 CERCA de la Generalitat de Catalunya. L’any 2009 es va convertir en un dels cinc primers centres d\u2019investigaci\u00f3 espanyols acreditats com a institut d\u2019investigaci\u00f3 sanit\u00e0ria per l\u2019Instituto de Salud Carlos III. A m\u00e9s, forma part del programa \u201cHR Excellence in Research\u201d de la Uni\u00f3 Europea i \u00e9s membre de EATRIS i REGIC. Des de l\u2019any 2018, l\u2019IDIBELL \u00e9s un Centro Acreditado de la Fundaci\u00f3n Cient\u00edfica AECC (FCAECC).<\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Un estudi liderat per l\u2019Institut d\u2019Investigaci\u00f3 Biom\u00e8tica de Bellvitge (IDIBELL) i la Universitat de Barcelona (UB) revela que la prote\u00efna TDP-43 \u00e9s essencial per formar una xarxa de vasos sanguinis estable i madura en el sistema nervi\u00f3s central.<\/p>\n","protected":false},"author":8,"featured_media":25228,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","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":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center 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