Les synucl\u00e9inopathies sont des maladies neurod\u00e9g\u00e9n\u00e9ratives caract\u00e9ris\u00e9es par l\u2019accumulation d\u2019une prot\u00e9ine appel\u00e9e \u03b1-synucl\u00e9ine sous forme agr\u00e9g\u00e9e au sein des cellules du syst\u00e8me nerveux central. La maladie de Parkinson est la synucl\u00e9inopathie la plus r\u00e9pandue, avec une accumulation de l\u2019\u03b1-synucl\u00e9ine localis\u00e9e au sein des neurones. L\u2019atrophie multisyst\u00e9matis\u00e9e est la seconde synucl\u00e9inopathie la plus r\u00e9pandue, caract\u00e9ris\u00e9e par l\u2019accumulation de l\u2019\u03b1-synucl\u00e9ine au sein des cellules protectrices des neurones, appel\u00e9es oligodendrocytes. L\u2019accumulation de cette prot\u00e9ine sous forme pathologique dans ces cellules joue un r\u00f4le important dans la mort des neurones. Dans cet article, nous avons adopt\u00e9 une strat\u00e9gie th\u00e9rapeutique ayant pour but d\u2019augmenter l\u2019\u00e9limination de l\u2019\u03b1-synucl\u00e9ine gr\u00e2ce \u00e0 l\u2019activation d\u2019un des syst\u00e8mes de d\u00e9gradation des prot\u00e9ines, appel\u00e9 autophagie, par l\u2019interm\u00e9diaire de la prot\u00e9ine TFEB. Pour ce faire, nous avons cibl\u00e9 sp\u00e9cifiquement les cellules affect\u00e9es dans des mod\u00e8les animaux de la maladie de Parkinson et d\u2019atrophie multisyst\u00e9matis\u00e9e. Nous avons d\u00e9montr\u00e9 qu\u2019un ciblage sp\u00e9cifique dans les neurones pour la maladie de Parkinson et dans les oligodendrocytes pour l\u2019atrophie multisyst\u00e9matis\u00e9e s\u2019av\u00e8re \u00eatre une strat\u00e9gie efficace pour prot\u00e9ger la mort des neurones. Ainsi, nous avons pu montrer pour la premi\u00e8re fois l\u2019int\u00e9r\u00eat de jouer sur sa d\u00e9gradation et de cibler sp\u00e9cifiquement les cellules o\u00f9 l\u2019\u03b1-synucl\u00e9ine s\u2019agr\u00e8ge comme piste th\u00e9rapeutique int\u00e9ressante pour ces maladies neurod\u00e9g\u00e9n\u00e9ratives.<\/p>\n
Synucleinopathies are neurodegenerative diseases characterized by the cellular accumulation of a protein called \u03b1-synuclein, in its misfolded conformation, into the central nervous system. Parkinson\u2019s disease is the most common synucleinopathy, characterized by a neuronal \u03b1-synuclein accumulation while Multiple System Atrophy, the second most prevalent synucleinopathy, is characterized by the accumulation of the protein in the oligodendrocytes, the neuronal protective cells. Misfolded \u03b1-synuclein cellular accumulation plays a major pathological role in neuronal cell loss. In this article, we adopted a strategy aiming to increase \u03b1-synuclein clearance via the activation of the protein degradation machinery – called autophagy – in the affected cells using rodent models of Parkinson\u2019s disease and Multiple System Atrophy. We showed that targeting the neuronal cells for Parkinson\u2019s disease or the oligodendrocytes for Multiple System Atrophy cases is an efficient strategy to induce neuroprotection. Thus, we demonstrated for the first time that targeting \u03b1-synuclein degradation in a cell-specific way according to the synucleinopathy, is a promising therapeutic strategy for these neurodegenerative diseases.<\/p>\n
Pour en savoir plus:<\/p>\n
Arotcarena ML, Bourdenx M, Dutheil N, Thiolat ML, Doudnikoff E, Dovero S, Ballabio A, Fernagut PO, Meissner WG, Bezard E, Dehay B. Transcription factor EB overexpression prevents neurodegeneration in experimental synucleinopathies. JCI\u00a0 Insight. 2019 Aug 22;4(16). pii: 129719. doi: 10.1172\/jci.insight.129719.<\/p>\n
<\/p>\n
Contact chercheur:<\/p>\n
Benjamin Dehay, Ph.D<\/p>\n
Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives (IMN), CNRS UMR 5293, Universit\u00e9 de Bordeaux<\/p>\n
benjamin.dehay@u-bordeaux.fr<\/p>\n","protected":false},"excerpt":{"rendered":"
Les synucl\u00e9inopathies sont des maladies neurod\u00e9g\u00e9n\u00e9ratives caract\u00e9ris\u00e9es par l\u2019accumulation d\u2019une prot\u00e9ine appel\u00e9e \u03b1-synucl\u00e9ine sous forme agr\u00e9g\u00e9e au sein des cellules du syst\u00e8me nerveux central. La maladie de Parkinson est la synucl\u00e9inopathie la plus r\u00e9pandue, avec une accumulation de l\u2019\u03b1-synucl\u00e9ine localis\u00e9e au sein des neurones. L\u2019atrophie multisyst\u00e9matis\u00e9e est la seconde synucl\u00e9inopathie la plus r\u00e9pandue, caract\u00e9ris\u00e9e par […]<\/p>\n","protected":false},"author":4,"featured_media":12069,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[31],"class_list":["post-12074","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-actualite-en"],"publishpress_future_action":{"enabled":false,"date":"2026-04-24 12:18:24","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/12074","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/comments?post=12074"}],"version-history":[{"count":1,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/12074\/revisions"}],"predecessor-version":[{"id":12075,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/12074\/revisions\/12075"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media\/12069"}],"wp:attachment":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media?parent=12074"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/categories?post=12074"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/tags?post=12074"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}