{"id":857,"date":"2025-06-23T16:07:19","date_gmt":"2025-06-23T14:07:19","guid":{"rendered":"https:\/\/imn-prod.onlinecreation.pro\/?p=857"},"modified":"2025-06-23T16:07:19","modified_gmt":"2025-06-23T14:07:19","slug":"des-assemblages-distincts-d%ce%b1-synucleine-declenchent-des-voies-cellulaires-neurotoxiques-distinctes","status":"publish","type":"post","link":"https:\/\/imn.u-bordeaux.fr\/fr\/2025\/06\/23\/des-assemblages-distincts-d%ce%b1-synucleine-declenchent-des-voies-cellulaires-neurotoxiques-distinctes\/","title":{"rendered":"Des assemblages distincts d&rsquo;\u03b1-synucl\u00e9ine d\u00e9clenchent des voies cellulaires neurotoxiques distinctes"},"content":{"rendered":"<div id=\"attachment_185037\" style=\"width: 370px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-185037\" class=\"wp-image-185037 size-medium\" src=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2025\/06\/Figure-Kinet_v1-360x304.png\" alt=\"\" width=\"360\" height=\"304\" \/><p id=\"caption-attachment-185037\" class=\"wp-caption-text\"><em>Chez les primates non-humains, les agr\u00e9gats d&rsquo;alpha-synucl\u00e9ine, qu\u2019ils soient larges (LA) ou petits (SA), induisent des m\u00e9canismes pathologiques distincts (\u00ab\u00a0pathogenic signature #1\u00a0\u00bb et \u00ab\u00a0pathogenic signature #2\u00a0\u00bb); tous menant \u00e0 la mort des neurones dopaminergiques.<\/em><\/p><\/div>\n<p><strong>Bordeaux, Juin 2025 &#8211; <\/strong>La maladie de Parkinson est une maladie neurod\u00e9g\u00e9n\u00e9rative caract\u00e9ris\u00e9e, entre autres, par la perte des neurones \u00e0 dopamine de la <em>substantia nigra pars compacta<\/em>. La disparition de ces neurones participe \u00e0 la pr\u00e9sentation clinique de cette maladie. En parall\u00e8le de cette d\u00e9g\u00e9n\u00e9rescence, nous retrouvons des agr\u00e9gats prot\u00e9iques, appel\u00e9s \u00ab\u00a0corps de Lewy\u00a0\u00bb, contenant de l\u2019alpha-synucl\u00e9ine dans le cerveau des patients atteints de cette maladie. Lors d\u2019une \u00e9tude pr\u00e9c\u00e9dente, nous avions montr\u00e9 que l\u2019isolation et l\u2019injection chez le rongeur ou le primate de ces agr\u00e9gats permettaient l\u2019initiation d\u2019une cascade pathologique r\u00e9capitulant certains aspects de la pathologie humaine.<\/p>\n<p>Afin de comprendre les m\u00e9canismes pathologiques engag\u00e9s par l\u2019injection des diff\u00e9rentes esp\u00e8ces d\u2019alpha-synucl\u00e9ine, nous avons cherch\u00e9 \u00e0 \u00e9lucider les changements pathologiques temporels et spatiaux induits par deux structures pathog\u00e8nes \u03b1-syn distinctes, de grande ou de petite taille. Ensuite, afin d&rsquo;\u00e9lucider les voies mol\u00e9culaires sous-jacentes, nous avons effectu\u00e9 une analyse prot\u00e9omique du putamen et du cortex entorhinal, deux r\u00e9gions c\u00e9r\u00e9brales pr\u00e9sentant une pathologie \u03b1-syn significative. Nous d\u00e9montrons que des assemblages distincts d&rsquo;agr\u00e9gats d&rsquo;\u03b1-syn entra\u00eenent des changements pathog\u00e8nes uniques qui aboutissent finalement \u00e0 une d\u00e9g\u00e9n\u00e9rescence nigrostriatale d&rsquo;ampleur comparable au niveau des corps cellulaires des neurones dopaminergiques nigraux et des terminaisons dopaminergiques striatales. De mani\u00e8re plus g\u00e9n\u00e9rale, nos r\u00e9sultats identifient des trajectoires pathog\u00e8nes associ\u00e9es \u00e0 des agr\u00e9gats d&rsquo;\u03b1-syn petits ou grands, sugg\u00e9rant l&rsquo;existence de plusieurs voies pathog\u00e8nes concomitantes possibles dans la maladie de Parkinson.<\/p>\n<h3>R\u00e9f\u00e9rence<\/h3>\n<p><strong>Differential Pathological Dynamics triggered by distinct Parkinson patient-derived \u03b1-synuclein extracts in non-human primates. <\/strong><\/p>\n<p><strong>Kinet R<\/strong>, Bourdenx M, <strong>Dovero S<\/strong>, <strong>Darricau M<\/strong>, <strong>Arotcarena ML<\/strong>, Camus S, Porras G, <strong>Thiolat ML<\/strong>, I. Trigo-Damas I, Bohic S, Morari M, <strong>Doudnikoff E<\/strong>, Goikoetxea M, Claverol S, Tokarski C, Kruse N, Mollenhauer B, Estrada C, Garcia-Carrillo N, Herrero MT, Vila M, Obeso JA, <strong>Bezard E, Dehay B<\/strong>.<br \/>\nSci. Adv.11,eadu6050(2025).DOI:10.1126\/sciadv.adu6050<\/p>\n<p><a href=\"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adu6050\">Lire la publication<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>R\u00e9mi Kinet et al. dans Science Advances<\/p>\n","protected":false},"author":8,"featured_media":858,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5,1],"tags":[],"class_list":["post-857","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-quoi-de-neuf","category-whats-new"],"_links":{"self":[{"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/posts\/857","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/comments?post=857"}],"version-history":[{"count":1,"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/posts\/857\/revisions"}],"predecessor-version":[{"id":860,"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/posts\/857\/revisions\/860"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/media\/858"}],"wp:attachment":[{"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/media?parent=857"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/categories?post=857"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/imn.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/tags?post=857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}