{"id":110595,"date":"2019-08-28T13:48:49","date_gmt":"2019-08-28T11:48:49","guid":{"rendered":"https:\/\/www.bordeaux-neurocampus.fr\/?p=110595"},"modified":"2019-09-16T14:52:23","modified_gmt":"2019-09-16T12:52:23","slug":"maria-florencia-angelo-and-etienne-herzog-in-acta-neuropathol","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/maria-florencia-angelo-and-etienne-herzog-in-acta-neuropathol\/","title":{"rendered":"Maria Florencia Angelo and Etienne Herzog in <em>Acta Neuropathol<\/em>"},"content":{"rendered":"<p><em>Early defects in translation elongation factor 1\u03b1 levels at excitatory synapses in \u03b1-synucleinopathy<\/em>. Blumenstock S., Angelo M.F., Peters F. et al. <em>Acta Neuropathol<\/em> (2019).<br \/>\n<a href=\"https:\/\/doi.org\/10.1007\/s00401-019-02063-3\">https:\/\/doi.org\/10.1007\/s00401-019-02063-3<\/a><\/p>\n<h2>Abstract<\/h2>\n<p>Cognitive decline and dementia in neurodegenerative diseases are associated with synapse dysfunction and loss, which may precede neuron loss by several years. While misfolded and aggregated \u03b1-synuclein is recognized in the disease progression of synucleinopathies, the nature of glutamatergic synapse dysfunction and loss remains incompletely understood. Using fluorescence-activated synaptosome sorting (FASS), we enriched excitatory glutamatergic synaptosomes from mice overexpressing human alpha-synuclein (h-\u03b1S) and wild-type littermates to unprecedented purity. Subsequent label-free proteomic quantification revealed a set of proteins differentially expressed upon human alpha-synuclein overexpression. These include overrepresented proteins involved in the synaptic vesicle cycle, ER\u2013Golgi trafficking, metabolism and cytoskeleton. Unexpectedly, we found and validated a steep reduction of eukaryotic translation elongation factor 1 alpha (eEF1A1) levels in excitatory synapses at early stages of h-\u03b1S mouse model pathology. While eEF1A1 reduction correlated with the loss of postsynapses, its immunoreactivity was found on both sides of excitatory synapses. Moreover, we observed a reduction in eEF1A1 immunoreactivity in the cingulate gyrus neuropil of patients with Lewy body disease along with a reduction in PSD95 levels. Altogether, our results suggest a link between structural impairments underlying cognitive decline in neurodegenerative disorders and local synaptic defects. eEF1A1 may therefore represent a limiting factor to synapse maintenance.<\/p>\n<p>Dr <a href=\"\/?page_id=19956\">Etienne HERZOG<\/a> \u2013 <a href=\"mailto:etienne.herzog@u-bordeaux.fr\">etienne.herzog@u-bordeaux.fr<\/a><\/p>\n<p>&nbsp;<\/p>\n<figure id=\"attachment_110526\" aria-describedby=\"caption-attachment-110526\" style=\"width: 770px\" class=\"wp-caption alignnone\"><a href=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2019\/08\/Blumenstock-2019.png\" rel=\"lightbox[110595]\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-110526 size-large\" src=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2019\/08\/Blumenstock-2019-770x180.png\" alt=\"Identification of the protein eEF1\u03b1 at purified excitatory presynapses. \" width=\"770\" height=\"180\" srcset=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2019\/08\/Blumenstock-2019-770x180.png 770w, https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2019\/08\/Blumenstock-2019-360x84.png 360w\" sizes=\"auto, (max-width: 770px) 100vw, 770px\" \/><\/a><figcaption id=\"caption-attachment-110526\" class=\"wp-caption-text\">Identification of the protein eEF1\u03b1 at purified excitatory presynapses.<\/figcaption><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>Early defects in translation elongation factor 1\u03b1 levels at excitatory synapses in \u03b1-synucleinopathy. <\/p>\n","protected":false},"author":108,"featured_media":110589,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71],"tags":[],"class_list":["post-110595","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\/110595","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=110595"}],"version-history":[{"count":0,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/110595\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media\/110589"}],"wp:attachment":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media?parent=110595"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/categories?post=110595"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/tags?post=110595"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}