{"id":110426,"date":"2019-08-26T16:29:52","date_gmt":"2019-08-26T14:29:52","guid":{"rendered":"https:\/\/www.bordeaux-neurocampus.fr\/?p=110426"},"modified":"2019-09-27T12:45:16","modified_gmt":"2019-09-27T10:45:16","slug":"marie-laure-arotcarena-benjamin-dehay-et-al-in-jci-insight","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/marie-laure-arotcarena-benjamin-dehay-et-al-in-jci-insight\/","title":{"rendered":"Marie-Laure Arotcarena, Benjamin Dehay et al. in <em>JCI Insight<\/em>"},"content":{"rendered":"<p><a href=\"https:\/\/insight.jci.org\/articles\/view\/129719\">https:\/\/insight.jci.org\/articles\/view\/129719<\/a><\/p>\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31434803\">https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31434803<\/a><\/p>\n<p class=\"author-list\">Marie-Laure Arotcarena<sup>1,2<\/sup>, Mathieu Bourdenx<sup>1,2<\/sup>, Nathalie Dutheil<sup>1,2<\/sup>, Marie-Laure Thiolat<sup>1,2<\/sup>, Evelyne Doudnikoff<sup>1,2<\/sup>, Sandra Dovero<sup>1,2<\/sup>, Andrea Ballabio<sup>3,4,5<\/sup>, Pierre-Olivier Fernagut<sup>6<\/sup>, Wassilios G. Meissner<sup>1,2,7<\/sup>, Erwan Bezard<sup>1,2<\/sup> and Benjamin Dehay<sup>1,2<\/sup><\/p>\n<p class=\"affiliations\"><sup>1<\/sup> Universit\u00e9 de Bordeaux, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, UMR 5293, F-33000 Bordeaux, France.<br \/>\n<sup>2 <\/sup>CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, UMR 5293, F-33000 Bordeaux, France.<br \/>\n<sup>3 <\/sup>Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (Naples), Italy.<br \/>\n<sup>4 <\/sup>Department of Translational Medicine, Federico II University, Naples, Italy.<br \/>\n<sup>5 <\/sup>Department of Molecular and Human Genetics, Ian and Dan Duncan Neurological Research Institute, Baylor College of Medicine, Houston, Texas, USA.<br \/>\n<sup>6 <\/sup>Laboratoire de Neurosciences Exp\u00e9rimentales et Cliniques, INSERM U-1084, Universit\u00e9 de Poitiers, Poitiers, France.<br \/>\n<sup>7 <\/sup>Service de Neurologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.<\/p>\n<p><b>Authorship note:<\/b> MLA and MB contributed equally to this work.<\/p>\n<h3>Abstract<\/h3>\n<p>The synucleinopathies Parkinson\u2019s disease (PD) and Multiple system atrophy (MSA) \u2014 characterized by \u03b1-synuclein intracytoplasmic inclusions into, respectively, neurons and oligodendrocytes\u00a0\u2014 are associated with impairment of the autophagy-lysosomal pathways (ALP). Increased expression of the master regulator of ALP, transcription factor EB (TFEB), is hypothesized to promote the\u00a0clearance of WT \u03b1-synuclein and survival of dopaminergic neurons. Here, we explore the efficacy of targeted TFEB overexpression either in neurons or oligodendrocytes to reduce the pathological\u00a0burden of \u03b1-synuclein in a PD rat model and a MSA mouse model. While TFEB neuronal expression was sufficient to prevent neurodegeneration in the PD model, we show that only TFEB\u00a0oligodendroglial overexpression leads to neuroprotective effects in the MSA model. These beneficial effects were associated with a decreased accumulation of \u03b1-synuclein into oligodendrocytes\u00a0through recovery of the ALP machinery. Our study demonstrates that the cell type where \u03b1-synuclein aggregates dictates the target of TFEB overexpression in order to be protective, paving the\u00a0way for adapted therapies.<\/p>\n<h2><a href=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2019\/08\/dehay-129719-INS-RG-RV-3_ga_proof_364685.jpg\" rel=\"lightbox[110426]\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-110422 size-large\" src=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2019\/08\/dehay-129719-INS-RG-RV-3_ga_proof_364685-611x770.jpg\" alt=\"\" width=\"611\" height=\"770\" \/><\/a>Contact<\/h2>\n<p><a href=\"mailto:benjamin.dehay@u-bordeaux.fr\">benjamin.dehay@u-bordeaux.fr<\/a>.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Transcription factor EB overexpression prevents neurodegeneration in experimental synucleinopathies<\/p>\n","protected":false},"author":108,"featured_media":110421,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71],"tags":[],"class_list":["post-110426","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlight-en"],"_links":{"self":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/110426","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/users\/108"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/comments?post=110426"}],"version-history":[{"count":0,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/110426\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media\/110421"}],"wp:attachment":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media?parent=110426"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/categories?post=110426"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/tags?post=110426"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}