{"id":5127,"date":"2024-06-05T14:45:18","date_gmt":"2024-06-05T18:45:18","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/amyloidogenic-regions-in-beta-strands-ii-and-iii-modulate-the-aggregation-and-toxicity-of-sod1-in-living-cells\/"},"modified":"2024-12-03T14:58:38","modified_gmt":"2024-12-03T19:58:38","slug":"amyloidogenic-regions-in-beta-strands-ii-and-iii-modulate-the-aggregation-and-toxicity-of-sod1-in-living-cells","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/amyloidogenic-regions-in-beta-strands-ii-and-iii-modulate-the-aggregation-and-toxicity-of-sod1-in-living-cells\/","title":{"rendered":"Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells"},"content":{"rendered":"<h2 class=\"title\">Abstract<\/h2>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<p>Mutations in the protein superoxide dismutase-1 (SOD1) promote its misfolding and aggregation, ultimately causing familial forms of the debilitating neurodegenerative disease amyotrophic lateral sclerosis (ALS). Currently, over 220 (mostly missense) ALS-causing mutations in the SOD1 protein have been identified, indicating that common structural features are responsible for aggregation and toxicity. Using\u00a0<i>in silico<\/i>\u00a0tools, we predicted amyloidogenic regions in the ALS-associated SOD1-G85R mutant, finding seven regions throughout the structure. Introduction of proline residues into \u03b2-strands II (I18P) or III (I35P) reduced the aggregation propensity and toxicity of SOD1-G85R in cells, significantly more so than proline mutations in other amyloidogenic regions. The I18P and I35P mutations also reduced the capability of SOD1-G85R to template onto previously formed non-proline mutant SOD1 aggregates as measured by fluorescence recovery after photobleaching. Finally, we found that, while the I18P and I35P mutants are less structurally stable than SOD1-G85R, the proline mutants are less aggregation-prone during proteasome inhibition, and less toxic to cells overall. Our research highlights the importance of a previously underappreciated SOD1 amyloidogenic region in \u03b2-strand II (<sup>15<\/sup>QGIINF<sup>20<\/sup>) to the aggregation and toxicity of SOD1 in ALS mutants, and suggests that \u03b2-strands II and III may be good targets for the development of SOD1-associated ALS therapies.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-5127","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells - CCNA - CCNV<\/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:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/amyloidogenic-regions-in-beta-strands-ii-and-iii-modulate-the-aggregation-and-toxicity-of-sod1-in-living-cells\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells - 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