Une \u00e9quipe de chercheurs bas\u00e9e \u00e0 Lille (Inserm, Universit\u00e9 de Lille, Institut Pasteur de Lille, CHU de Lille), en collaboration avec l\u2019Universit\u00e9 de Finlande orientale, l\u2019Institut interdisciplinaire de neurosciences (CNRS, Universit\u00e9 de Bordeaux) et l\u2019Universit\u00e9 de Boston, publie dans la revue Nature Genetics des r\u00e9sultats nouveaux sur les m\u00e9canismes de la maladie d\u2019Alzheimer. Les travaux portent sur le g\u00e8ne PLCG2, d\u00e9j\u00e0 identifi\u00e9 comme associ\u00e9 au risque de d\u00e9velopper cette maladie, et montrent qu\u2019il joue un r\u00f4le cl\u00e9 dans le maintien des synapses, au-del\u00e0 de ce qui \u00e9tait jusqu\u2019\u00e0 pr\u00e9sent connu.<\/p>\n
Les chercheurs ont r\u00e9alis\u00e9 un criblage g\u00e9n\u00e9tique \u00e0 haut d\u00e9bit sur 198 g\u00e8nes associ\u00e9s au risque de maladie d\u2019Alzheimer afin d\u2019\u00e9valuer leur impact sur la densit\u00e9 synaptique. Neuf g\u00e8nes se sont r\u00e9v\u00e9l\u00e9s particuli\u00e8rement impliqu\u00e9s, dont PLCG2, qui appara\u00eet comme un acteur central. Jusqu\u2019ici surtout \u00e9tudi\u00e9 dans la microglie (cellules immunitaires du cerveau), PLCG2 est montr\u00e9 comme agissant aussi directement dans les neurones : une diminution de son expression entra\u00eene une baisse de la densit\u00e9 synaptique et de l\u2019activit\u00e9 \u00e9lectrique neuronale, ainsi qu\u2019une augmentation de la s\u00e9cr\u00e9tion de peptides \u03b2-amylo\u00efdes et de la production de prot\u00e9ine Tau anormalement phosphoryl\u00e9e, deux l\u00e9sions caract\u00e9ristiques de la maladie. Ces effets semblent r\u00e9versibles, la restauration de l\u2019expression de PLCG2 permettant un retour \u00e0 un fonctionnement proche de la normale.<\/p>\n
L\u2019\u00e9tude indique \u00e9galement que des variants rares de PLCG2 peuvent multiplier par dix le risque de d\u00e9velopper la maladie d\u2019Alzheimer. Des analyses sugg\u00e8rent un lien possible avec les neurexines, prot\u00e9ines d\u00e9j\u00e0 associ\u00e9es \u00e0 la toxicit\u00e9 synaptique des peptides \u03b2-amylo\u00efdes, m\u00eame si ce m\u00e9canisme reste \u00e0 pr\u00e9ciser. Les auteurs mettent en avant que ces r\u00e9sultats contribuent \u00e0 renouveler la compr\u00e9hension des m\u00e9canismes de la maladie, en compl\u00e9tant l\u2019hypoth\u00e8se de la \u00ab cascade amylo\u00efde \u00bb par des approches centr\u00e9es sur les synapses et les interactions g\u00e9n\u00e9tiques. Ils confirment aussi l\u2019importance des facteurs g\u00e9n\u00e9tiques dans une pathologie qui touche plus d\u2019un million de personnes en France et constitue un enjeu majeur de sant\u00e9 publique dans un contexte de vieillissement de la population. Aucun \u00e9l\u00e9ment de la source ne pr\u00e9cise cependant de mesure de sant\u00e9 publique imm\u00e9diate ni d\u2019application clinique directe, les r\u00e9sultats relevant \u00e0 ce stade de la recherche fondamentale.\u00a0(contenu r\u00e9sum\u00e9 par l’IA)\u200bLire la Suite<\/a>\u200b<\/p>","protected":false},"excerpt":{"rendered":" Une \u00e9quipe de chercheurs bas\u00e9e \u00e0 Lille (Inserm, Universit\u00e9 de Lille, Institut Pasteur de Lille, CHU de Lille), en collaboration avec l\u2019Universit\u00e9 de Finlande orientale, l\u2019Institut interdisciplinaire de neurosciences (CNRS, […]<\/p>\n","protected":false},"author":1,"featured_media":4209,"comment_status":"","ping_status":"","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":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center 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