{"id":126090,"date":"2025-05-30T11:13:18","date_gmt":"2025-05-30T09:13:18","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/disrupting-malarias-inner-balance-targeting-parasites-protein-control-system-could-be-key-to-innovative-treatments\/"},"modified":"2025-05-30T12:12:19","modified_gmt":"2025-05-30T10:12:19","slug":"disrupting-malarias-inner-balance-targeting-parasites-protein-control-system-could-be-key-to-innovative-treatments","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/alterar-el-control-de-proteines-del-parasit-pot-obrir-noves-vies-terapeutiques-contra-la-malaria","title":{"rendered":"Alterar el control de prote\u00efnes del par\u00e0sit pot obrir noves vies terap\u00e8utiques contra la mal\u00e0ria"},"content":{"rendered":"\n

Investigadors de l’IBEC i ISGlobal han dirigit un estudi que apunta a l’agregaci\u00f3 de prote\u00efnes com a possible diana per a trobar noves maneres de reduir la viabilitat del\u00a0Plasmodium\u00a0falciparum<\/em>, el principal agent causant de la mal\u00e0ria. En induir l’agregaci\u00f3 proteica, van observar trastorns considerables en l’home\u00f2stasi de les prote\u00efnes i una reducci\u00f3 significativa del creixement del par\u00e0sit. Els resultats situen el control de l’agregaci\u00f3 proteica com una diana prometedora per a les ter\u00e0pies\u00a0antimal\u00e0riques.<\/strong><\/p>\n\n\n\n

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Mosquit Anopheles minimus<\/em>, vector de la mal\u00e0ria a Orient, alimentant-se d’un hoste hum\u00e0. \/ Cr\u00e8dit: James Gathany<\/i><\/figcaption><\/figure>\n\n\n\n

La mal\u00e0ria continua sent una c\u00e0rrega persistent per a la salut p\u00fablica mundial, i el par\u00e0sit\u00a0Plasmodium\u00a0falciparum<\/em>\u00a0causa la forma m\u00e9s perillosa de la malaltia i les infeccions m\u00e9s letals. La seva capacitat per a desenvolupar resist\u00e8ncia als tractaments actuals subratlla la urg\u00e8ncia d’identificar noves dianes moleculars.<\/p>\n\n\n\n

En aquest context, un estudi recent liderat pel grup de recerca\u00a0Nanomalaria<\/a>\u00a0de l’Institut de Bioenginyeria de Catalunya (IBEC) i l’Institut de Salut Global de Barcelona (ISGlobal), ha descobert una potencial vulnerabilitat en P.\u00a0falciparum<\/em>\u00a0en induir l’agregaci\u00f3 de prote\u00efnes dins del par\u00e0sit. Els investigadors van induir la\u00a0sobreexpressi\u00f3\u00a0d’un segment espec\u00edfic d’una prote\u00efna intr\u00ednsecament desordenada, que va afectar significativament el creixement del par\u00e0sit. El treball, publicat en la revista\u00a0Frontiers\u00a0in\u00a0Cellular\u00a0and\u00a0Infection\u00a0Microbiology<\/a>, pot obrir la porta a noves estrat\u00e8gies\u00a0antimal\u00e0riques\u00a0dirigides a la maquin\u00e0ria interna de plegament de prote\u00efnes del par\u00e0sit.<\/p>\n\n\n\n

Descobriment d’un possible tal\u00f3 d’Aquil\u00b7les en els par\u00e0sits de la mal\u00e0ria<\/strong><\/h4>\n\n\n\n

El concepte d’agregaci\u00f3 de prote\u00efnes, que es refereix a l’acumulaci\u00f3 de prote\u00efnes mal plegades o desplegades en grups insolubles, ha estat fonamental en aquest estudi. En els \u00e9ssers humans, aquest proc\u00e9s s’associa a diverses malalties neurodegeneratives, com l’Alzheimer i el Parkinson, en les quals les prote\u00efnes agregades alteren les funcions cel\u00b7lulars i provoquen la seva mort. L’agregaci\u00f3 de prote\u00efnes sol contrarestar-se mitjan\u00e7ant\u00a0xaperones\u00a0moleculars i sistemes\u00a0proteasomals\u00a0que mantenen la\u00a0prote\u00f2stasi, un equilibri cel\u00b7lular essencial de s\u00edntesi, plegament i degradaci\u00f3 de prote\u00efnes.<\/p>\n\n\n\n

En P.\u00a0falciparum<\/em>, no obstant aix\u00f2, l’escenari \u00e9s particularment intrigant. D’una banda, el par\u00e0sit codifica una robusta xarxa de\u00a0prote\u00f2stasi\u00a0adaptada per a sobreviure als intensos canvis metab\u00f2lics i a les condicions d’estr\u00e8s que troba durant el seu cicle vital, tant a l’interior del seu vector, els mosquits del g\u00e8nere\u00a0Anopheles<\/em>, com en l’hoste hum\u00e0.<\/p>\n\n\n\n

\n

Al\u00a0sobreexpressar\u00a0un segment desordenat de\u00a0PfUT\u00a0en P.\u00a0falciparum<\/em>, alterem aquest fr\u00e0gil equilibri, desencadenant estr\u00e8s\u00a0proteot\u00f2xic\u00a0i provocant una reducci\u00f3 del creixement del par\u00e0sit.<\/p>\n\n\n\n

Yunuen Avalos-Padilla<\/p>\n<\/blockquote>\n\n\n\n

No obstant aix\u00f2, i contradict\u00f2riament, les prote\u00efnes de P. falciparum<\/em> s\u00f3n molt propenses a l’agregaci\u00f3. Malgrat el seu genoma relativament petit i el seu proteoma eficient, l’alta propensi\u00f3 a l’agregaci\u00f3 de prote\u00efnes en aquest organisme pot reflectir un comprom\u00eds evolutiu ben ajustat entre funcionalitat i inestabilitat. Aquesta propietat pot conferir al par\u00e0sit avantatges adaptatius espec\u00edfics, com contribuir a la protecci\u00f3 proteica o facilitar la formaci\u00f3 d’agregats relacionats amb l’estr\u00e8s que l’ajudin a sobreviure en entorns hostils, com la febre en l’hoste hum\u00e0 i l’estr\u00e8s oxidatiu en les c\u00e8l\u00b7lules infectades. En aquest sentit, posseeix una proporci\u00f3 relativament alta de prote\u00efnes amb regions intr\u00ednsecament desordenades – com la prote\u00efna ubiquitina ligasa, PfUT – que solen ser m\u00e9s propenses al mal plegament i l’agregaci\u00f3 sota estr\u00e8s.<\/p>\n\n\n\n

Aquest complex escenari\u00a0prote\u00f2mic\u00a0va portar els investigadors a explorar si un augment indu\u00eft d’una prote\u00efna molt abundant i propensa a l’agregaci\u00f3 com\u00a0PfUT\u00a0podria despla\u00e7ar el\u00a0proteoma\u00a0del par\u00e0sit cap a un estat d’agregaci\u00f3 que super\u00e9s la seva maquin\u00e0ria de control de la\u00a0prote\u00f2stasi, provocant una disminuci\u00f3 en la seva viabilitat.<\/p>\n\n\n\n

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Els dos primers panells mostren imatges de microsc\u00f2pia electr\u00f2nica de transmissi\u00f3 de gl\u00f2buls vermells infectats amb par\u00e0sits de la mal\u00e0ria: a l’esquerra, infectats pel par\u00e0sit de tipus salvatge (P.\u00a0falciparum<\/em>\u00a03D7), amb una estructura d’org\u00e0nuls normal; i a la dreta per la versi\u00f3\u00a0sobreexpressora\u00a0transg\u00e8nica (P.\u00a0falciparum<\/em>\u00a0UTf), amb un vac\u00faol alimentari engrandit i material electr\u00f3-dens en el citoplasma del gl\u00f2bul vermell circumdant. L’\u00faltim panell mostra que els par\u00e0sits mutants tenen un creixement m\u00e9s lent en comparaci\u00f3 amb el parental.<\/figcaption><\/figure>\n\n\n\n

“Al\u00a0sobreexpressar\u00a0un segment desordenat de\u00a0PfUT\u00a0en P.\u00a0falciparum<\/em>, alterem aquest fr\u00e0gil equilibri, desencadenant estr\u00e8s\u00a0proteot\u00f2xic\u00a0i provocant una reducci\u00f3 del creixement del par\u00e0sit. No obstant aix\u00f2, malgrat les alteracions observades en la\u00a0prote\u00f2stasi, els par\u00e0sits no van morir per l’augment de l’agregaci\u00f3 d’aquesta prote\u00efna en particular, la qual cosa demostra la seva capacitat per a controlar un\u00a0proteoma\u00a0altament propens a l’agregaci\u00f3”, explica\u00a0Yunuen\u00a0Avalos-Padilla, primera autora del treball.<\/p>\n\n\n\n

\n

Aquest estudi no sols posa de manifest una vulnerabilitat clau en el sistema intern de gesti\u00f3 de prote\u00efnes de\u00a0Plasmodium\u00a0falciparum<\/em>, sin\u00f3 que tamb\u00e9 posiciona el control de l’agregaci\u00f3 de prote\u00efnes com un objectiu prometedor per a la intervenci\u00f3\u00a0antimal\u00e0rica.<\/p>\n\n\n\n

Xavier Fern\u00e1ndez-Busquets<\/p>\n<\/blockquote>\n\n\n\n

En altres paraules, en sobrecarregar el sistema de prote\u00f2stasi del par\u00e0sit, els investigadors van aconseguir comprometre la seva superviv\u00e8ncia, encara que el Plasmodium<\/em> es va poder recuperar.<\/p>\n\n\n\n

Aquest descobriment identifica un aspecte nou i potencialment explotable de la biologia del par\u00e0sit: la seva susceptibilitat a les alteracions en el control de l’agregaci\u00f3 de prote\u00efnes. Per tant, les estrat\u00e8gies terap\u00e8utiques que amplifiquen el mal plegament d’unes certes prote\u00efnes clau o bloquegen la capacitat del par\u00e0sit per a respondre a l’agregaci\u00f3 podrien oferir una nova i eficient l\u00ednia d’atac.<\/p>\n\n\n\n

En paraules de Fern\u00e0ndez-Busquets, “aquest estudi no sols posa de manifest una vulnerabilitat clau en el sistema intern de gesti\u00f3 de prote\u00efnes de Plasmodium falciparum<\/em>, sin\u00f3 que tamb\u00e9 posiciona el control de l’agregaci\u00f3 de prote\u00efnes com un objectiu prometedor per a la intervenci\u00f3 antimal\u00e0rica. En aprofundir en el coneixement dels mecanismes de prote\u00f2stasi del par\u00e0sit, podem obrir noves vies per a combatre una de les malalties infeccioses m\u00e9s persistents del m\u00f3n”.<\/p>\n\n\n\n

No obstant aix\u00f2, passar dels resultats de laboratori a l’aplicaci\u00f3 cl\u00ednica requereix m\u00e9s treball. Els estudis futurs hauran de dilucidar les interaccions moleculars precises implicades i determinar si existeixen vulnerabilitats similars en les diferents fases de vida del par\u00e0sit. A m\u00e9s, qualsevol compost que es desenvolupi per a explotar aquest mecanisme haur\u00e0 d’avaluar-se acuradament per a garantir la seva selectivitat i seguretat.<\/p>\n\n\n\n

\n\n\n\n

Article de refer\u00e8ncia:<\/strong><\/p>\n\n\n\n

Yunuen Avalos-Padilla, In\u00e9s Bouz\u00f3n-Arn\u00e1iz, Miriam Ram\u00edrez, Claudia Camarero-Hoyos, Marc Orozco-Quer, Elsa M. Arce, Diego Mu\u00f1oz-Torrero and Xavier Fern\u00e0ndez-Busquets. Overexpression in Plasmodium falciparum<\/em> of an intrinsically disordered protein segment of PfUT impairs the parasite\u2019s proteostasis and reduces its growth rate<\/strong>. <\/em><\/strong>Front. Cell. Infect. Microbiol<\/em>. Volume 15 – 2025. doi: 10.3389\/fcimb.2025.1565814<\/a><\/em><\/strong><\/p>\n\n\n\n

\n","protected":false},"excerpt":{"rendered":"

Investigadors de l’IBEC i ISGlobal han dirigit un estudi que apunta a l’agregaci\u00f3 de prote\u00efnes com a possible diana per a trobar noves maneres de reduir la viabilitat del Plasmodium falciparum, el principal agent causant de la mal\u00e0ria. En induir l’agregaci\u00f3 proteica, van observar trastorns considerables en l’home\u00f2stasi de les prote\u00efnes i una reducci\u00f3 significativa del creixement del par\u00e0sit. Els resultats situen el control de l’agregaci\u00f3 proteica com una diana prometedora per a les ter\u00e0pies antimal\u00e0riques.<\/p>\n","protected":false},"author":37,"featured_media":126084,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[312,2105,2103,313,1112],"post_formats":[],"class_list":["post-126090","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-malaria-ca-2","tag-nanomalaria-ca","tag-nanomalaria-grup","tag-plasmodium-falciparum-ca","tag-xavier-fernandez-busquets-ca"],"yoast_head":"\nAlterar el control de prote\u00efnes del par\u00e0sit pot obrir noves vies terap\u00e8utiques contra la mal\u00e0ria - 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\/alterar-el-control-de-proteines-del-parasit-pot-obrir-noves-vies-terapeutiques-contra-la-malaria\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Alterar el control de prote\u00efnes del par\u00e0sit pot obrir noves vies terap\u00e8utiques contra la mal\u00e0ria - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadors de l'IBEC i ISGlobal han dirigit un estudi que apunta a l'agregaci\u00f3 de prote\u00efnes com a possible diana per a trobar noves maneres de reduir la viabilitat del Plasmodium falciparum, el principal agent causant de la mal\u00e0ria. En induir l'agregaci\u00f3 proteica, van observar trastorns considerables en l'home\u00f2stasi de les prote\u00efnes i una reducci\u00f3 significativa del creixement del par\u00e0sit. 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