{"id":11631,"date":"2025-11-12T17:52:25","date_gmt":"2025-11-12T16:52:25","guid":{"rendered":"https:\/\/rvh-synergie.org\/actualites\/les-resultats-revelent-le-role-de-fbxo21-dans-la-degenerescence-des-axones\/"},"modified":"2025-11-12T17:52:44","modified_gmt":"2025-11-12T16:52:44","slug":"les-resultats-revelent-le-role-de-fbxo21-dans-la-degenerescence-des-axones","status":"publish","type":"post","link":"https:\/\/rvh-synergie.org\/actualites\/les-resultats-revelent-le-role-de-fbxo21-dans-la-degenerescence-des-axones\/","title":{"rendered":"Les r\u00e9sultats r\u00e9v\u00e8lent le r\u00f4le de FBXO21 dans la d\u00e9g\u00e9n\u00e9rescence des axones"},"content":{"rendered":"
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NMNAT2 est une prot\u00e9ine cl\u00e9 n\u00e9cessaire \u00e0 l’int\u00e9grit\u00e9 des axones dont l’\u00e9puisement rapide suite \u00e0 une l\u00e9sion axonale d\u00e9clenche la d\u00e9g\u00e9n\u00e9rescence wall\u00e9rienne. Le m\u00e9canisme mol\u00e9culaire contr\u00f4lant le renouvellement de NMNAT2 dans les neurones n\u2019a pas \u00e9t\u00e9 enti\u00e8rement compris. On pense que la d\u00e9gradation de NMNAT2 est acc\u00e9l\u00e9r\u00e9e dans les axones en cas de blessure et que NMNAT2 pourrait avoir des m\u00e9canismes de r\u00e9gulation diff\u00e9rents dans le soma neuronal et les axones.<\/p>\n

Dans une \u00e9tude publi\u00e9e en ligne dans Journal de biologie cellulaire<\/i>une \u00e9quipe de recherche dirig\u00e9e par le professeur Fang Yanshan de l’Institut de chimie organique de Shanghai de l’Acad\u00e9mie chinoise des sciences a identifi\u00e9 FBXO21 comme la prot\u00e9ine F-box et le facteur cl\u00e9 m\u00e9diant l’ubiquitination et la d\u00e9gradation de NMNAT2 dans les neurones, et a d\u00e9couvert que l’inactivation de Fbxo21 dans les neurones du ganglion de la racine dorsale de souris augmente les niveaux de NMNAT2 et retarde consid\u00e9rablement la d\u00e9g\u00e9n\u00e9rescence wall\u00e9rienne.<\/p>\n

Les chercheurs ont d\u2019abord d\u00e9montr\u00e9 que le taux de renouvellement de la prot\u00e9ine NMNAT2 dans le soma et les axones, ainsi qu\u2019avant et apr\u00e8s une blessure, est comparable, ce qui sugg\u00e8re un m\u00e9canisme unifi\u00e9 contr\u00f4lant la d\u00e9gradation de NMNAT2.<\/p>\n

Ils ont ensuite d\u00e9couvert que l\u2019\u00e9puisement rapide de NMNAT2 dans les axones bless\u00e9s est principalement d\u00fb au manque d\u2019approvisionnement en prot\u00e9ine NMNAT2 nouvellement synth\u00e9tis\u00e9e \u00e0 partir du soma. Il a \u00e9t\u00e9 constat\u00e9 que FBXO21 r\u00e9gulait la stabilit\u00e9 de NMNAT2 et l’int\u00e9grit\u00e9 des axones dans le soma et l’axone, qu’ils soient bless\u00e9s ou non.<\/p>\n

\u00c0 l\u2019aide de tests d\u2019immunopr\u00e9cipitation d\u00e9naturante et d\u2019ubiquitination in vitro, les chercheurs ont d\u00e9montr\u00e9 que FBXO21 interagissait avec SKP1, CUL1 et RBX1 pour former un SCF.FBXO21<\/sup> Complexe E3 ligase qui m\u00e9die l’ubiquitination de NMNAT2.<\/p>\n

Ils ont d\u00e9couvert que SCFFBXO21<\/sup> NMNAT2 ubiquitin\u00e9 au niveau de K155 dans le domaine de ciblage et d’interaction sp\u00e9cifique \u00e0 l’isoforme (ISTID) et la mutation K155R d\u00e9ficiente en ubiquitination ont prolong\u00e9 de mani\u00e8re significative la demi-vie de NMNAT2 et am\u00e9lior\u00e9 consid\u00e9rablement sa protection axonale.<\/p>\n

Fait int\u00e9ressant, les chercheurs ont d\u00e9couvert que l\u2019\u00e9change de l\u2019ISTID de NMNAT1 ou NMNAT3 avec celui de NMNAT2 entra\u00eenait une d\u00e9gradation rapide des prot\u00e9ines initialement tr\u00e8s stables, tandis que l\u2019introduction de la mutation K155R \u00e9liminait cet effet. Ces r\u00e9sultats ont mis en \u00e9vidence l’ubiquitination de K155 au sein de l’ISTID comme un d\u00e9terminant \u00e9volutif cl\u00e9 de la demi-vie ultra-courte de NMNAT2, r\u00e9v\u00e9lant la base mol\u00e9culaire et structurelle de la labilit\u00e9 unique de NMNAT2.<\/p>\n

Enfin, les chercheurs ont g\u00e9n\u00e9r\u00e9 des souris knock-out Fbxo21 et ont r\u00e9v\u00e9l\u00e9 que les niveaux de prot\u00e9ine NMNAT2 \u00e9taient sp\u00e9cifiquement \u00e9lev\u00e9s dans le syst\u00e8me nerveux. En utilisant un mod\u00e8le de l\u00e9sion du nerf sciatique chez la souris, ils ont d\u00e9montr\u00e9 que l\u2019inactivation de Fbxo21 retardait consid\u00e9rablement la d\u00e9g\u00e9n\u00e9rescence wall\u00e9rienne in vivo.<\/p>\n

L’\u00e9tude r\u00e9v\u00e8le que FBXO21 joue un r\u00f4le cl\u00e9 dans la r\u00e9gulation de la stabilit\u00e9 de NMNAT2 et d\u00e9montre que la d\u00e9couverte de la prot\u00e9ine FBXO21 d\u00e9terminant le substrat pour NMNAT2 est particuli\u00e8rement significative. Il fournit une cible potentielle et une strat\u00e9gie d’intervention pour am\u00e9liorer la survie des axones d\u00e9pendants de NMNAT2 dans les l\u00e9sions neuronales et les maladies d\u00e9g\u00e9n\u00e9ratives.<\/p>\n

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

NMNAT2 est une prot\u00e9ine cl\u00e9 n\u00e9cessaire \u00e0 l’int\u00e9grit\u00e9 des axones dont l’\u00e9puisement rapide suite \u00e0<\/p>\n","protected":false},"author":1,"featured_media":11632,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86],"tags":[7646,44,2870,16,7645,49,69,149,2411],"class_list":["post-11631","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-les-maladies","tag-axones","tag-dans","tag-degenerescence","tag-des","tag-fbxo21","tag-les","tag-resultats","tag-revelent","tag-role","generate-columns","tablet-grid-50","mobile-grid-100","grid-parent","grid-50","resize-featured-image"],"yoast_head":"\nLes r\u00e9sultats r\u00e9v\u00e8lent le r\u00f4le de FBXO21 dans la d\u00e9g\u00e9n\u00e9rescence des axones - RVH-Synergie.org<\/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:\/\/rvh-synergie.org\/actualites\/les-resultats-revelent-le-role-de-fbxo21-dans-la-degenerescence-des-axones\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Les r\u00e9sultats r\u00e9v\u00e8lent le r\u00f4le de FBXO21 dans la d\u00e9g\u00e9n\u00e9rescence des axones - 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