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A large body of evidence implicates dipeptide repeats (DPRs) proteins as one of the main drivers of neuronal injury in cell and animal models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A pure repeat\u2010associated non\u2010AUG (RAN) translation zebrafish model of C9orf72\u2010ALS\/FTD was generated. Embryonic and adult transgenic zebrafish lysates were investigated for the presence of RAN\u2010translated DPR species and adult\u2010onset motor deficits. Using C9orf72 cell models as well as embryonic C9orf72\u2010ALS\/FTD zebrafish, hypothermic\u2010therapeutic temperature management (TTM) was explored as a potential therapeutic option for C9orf72\u2010ALS\/FTD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we describe a pure RAN translation zebrafish model of C9orf72\u2010ALS\/FTD that exhibits significant RAN\u2010translated DPR pathology and progressive motor decline. We further demonstrate that hypothermic\u2010TTM results in a profound reduction in DPR species in C9orf72\u2010ALS\/FTD cell models as well as embryonic C9orf72\u2010ALS\/FTD zebrafish.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>The transgenic model detailed in this paper provides a medium throughput in vivo research tool to further investigate the role of RAN\u2010translation in C9orf72\u2010ALS\/FTD and further understand the mechanisms that underpin neuroprotective strategies. Hypothermic\u2010TTM presents a viable therapeutic avenue to explore in the context of C9orf72\u2010ALS\/FTD. ANN NEUROL 2024;96:1058\u20131069<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27068","type":"journal-article","created":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T09:10:05Z","timestamp":1725095405000},"page":"1058-1069","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>RAN<\/scp>\n                    Translation of C9orf72\u2010Related Dipeptide Repeat Proteins in Zebrafish Recapitulates Hallmarks of Amyotrophic Lateral Sclerosis and Identifies Hypothermia as a Therapeutic Strategy"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5833-9379","authenticated-orcid":false,"given":"David J.","family":"Burrows","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, Division of Neuroscience University of Sheffield  Sheffield 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