{"id":4574,"date":"2022-04-07T08:41:45","date_gmt":"2022-04-07T07:41:45","guid":{"rendered":"https:\/\/ibb.uab.cat\/?p=4574"},"modified":"2022-04-07T08:48:51","modified_gmt":"2022-04-07T07:48:51","slug":"ppdp_jbc","status":"publish","type":"post","link":"https:\/\/ibb.uab.cat\/index.php\/2022\/04\/07\/ppdp_jbc\/","title":{"rendered":"Protein Folding and Conformational Diseases: &#8220;The small aromatic compound SynuClean-D inhibits the aggregation and seeded polymerization of multiple \u03b1-synuclein strains&#8221;"},"content":{"rendered":"\n<div class=\"wp-block-image is-style-rounded\"><figure class=\"alignleft size-large\"><img loading=\"lazy\" width=\"369\" height=\"132\" src=\"https:\/\/ibb.uab.cat\/wp-content\/uploads\/jbc.jpg\" alt=\"\" class=\"wp-image-4575\" srcset=\"https:\/\/ibb.uab.cat\/wp-content\/uploads\/jbc.jpg 369w, https:\/\/ibb.uab.cat\/wp-content\/uploads\/jbc-300x107.jpg 300w, https:\/\/ibb.uab.cat\/wp-content\/uploads\/jbc-367x132.jpg 367w\" sizes=\"(max-width: 369px) 100vw, 369px\" \/><\/figure><\/div>\n\n\n\n<p>Available online 4 April 2022, 101902<\/p>\n\n\n\n<p><a href=\"https:\/\/doi.org\/10.1016\/j.jbc.2022.101902\">https:\/\/doi.org\/10.1016\/j.jbc.2022.101902<\/a><\/p>\n\n\n\n<p><\/p>\n\n\n\n<pre class=\"wp-block-verse\"><\/pre>\n\n\n\n<hr class=\"wp-block-separator\"\/>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignright size-large is-resized\"><img loading=\"lazy\" src=\"https:\/\/ibb.uab.cat\/wp-content\/uploads\/X00219258.jpg\" alt=\"\" class=\"wp-image-4576\" width=\"373\" height=\"491\" srcset=\"https:\/\/ibb.uab.cat\/wp-content\/uploads\/X00219258.jpg 583w, https:\/\/ibb.uab.cat\/wp-content\/uploads\/X00219258-228x300.jpg 228w, https:\/\/ibb.uab.cat\/wp-content\/uploads\/X00219258-197x260.jpg 197w\" sizes=\"(max-width: 373px) 100vw, 373px\" \/><\/figure><\/div>\n\n\n\n<p><\/p>\n\n\n\n<h2 class=\"has-huge-font-size\">Abstract<\/h2>\n\n\n\n<p id=\"abspara0010\">Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the <em>substantia nigra<\/em>, as well as the accumulation of intra-neuronal proteinaceous inclusions known as Lewy bodies and Lewy neurites. The major protein component of Lewy inclusions is the intrinsically disordered protein \u03b1-Synuclein (\u03b1-Syn), which can adopt diverse amyloid structures. Different conformational strains of \u03b1-Syn have been proposed to be related to the onset of distinct synucleinopathies; however, how specific amyloid fibrils cause distinctive pathological traits is not clear. Here, we generated three different \u03b1-Syn amyloid conformations at different pH and salt concentrations and analyzed the activity of SynuClean-D (SC-D), a small aromatic molecule, on these strains. We show that incubation of \u03b1-Syn with SC-D reduced the formation of aggregates and the seeded polymerization of \u03b1-Syn in all cases. Moreover, we found that SC-D exhibited a general fibril disaggregation activity. Finally, we demonstrate that treatment with SC-D also reduced strain-specific intracellular accumulation of phosphorylated \u03b1-Syn inclusions. Taken together, we conclude that SC-D may be a promising hit compound to inhibit polymorphic \u03b1-Syn aggregation.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<p>Samuel Pe\u00f1a-D\u00edaz; Jordi Pujols; Eftychia Vasili; Francisca Pinheiro; Jaime Santos; Zoe Manglano-Artu\u00f1edo; Tiago F. Outeiro; Salvador Ventura<\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Available online 4 April 2022, 101902 https:\/\/doi.org\/10.1016\/j.jbc.2022.101902 Abstract Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, as well as the accumulation of intra-neuronal proteinaceous inclusions known as Lewy bodies and Lewy neurites. The major protein component of Lewy inclusions is the intrinsically disordered protein \u03b1-Synuclein [&hellip;]<\/p>\n","protected":false},"author":65,"featured_media":4576,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[4],"tags":[],"_links":{"self":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/4574"}],"collection":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/comments?post=4574"}],"version-history":[{"count":5,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/4574\/revisions"}],"predecessor-version":[{"id":4585,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/4574\/revisions\/4585"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media\/4576"}],"wp:attachment":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media?parent=4574"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/categories?post=4574"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/tags?post=4574"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}