{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:30:35Z","timestamp":1773768635103,"version":"3.50.1"},"reference-count":180,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["PLEC2022-009367"],"award-info":[{"award-number":["PLEC2022-009367"]}]},{"name":"European Union","award":["PLEC2022-009367"],"award-info":[{"award-number":["PLEC2022-009367"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drosophila melanogaster usage has provided substantial insights into the pathogenesis of several nucleotide repeat expansion diseases (NREDs), a group of genetic diseases characterized by the abnormal expansion of DNA repeats. Leveraging the genetic simplicity and manipulability of Drosophila, researchers have successfully modeled close to 15 NREDs such as Huntington\u2019s disease (HD), several spinocerebellar ataxias (SCA), and myotonic dystrophies type 1 and 2 (DM1\/DM2). These models have been instrumental in characterizing the principal associated molecular mechanisms: protein aggregation, RNA toxicity, and protein function loss, thus recapitulating key features of human disease. Used in chemical and genetic screenings, they also enable us to identify promising small molecules and genetic modifiers that mitigate the toxic effects of expanded repeats. This review summarizes the close to 150 studies performed in this area during the last seven years. The relevant highlights are the achievement of the first fly-based models for some NREDs, the incorporation of new technologies such as CRISPR for developing or evaluating transgenic flies containing repeat expanded motifs, and the evaluation of less understood toxic mechanisms in NREDs such as RAN translation. Overall, Drosophila melanogaster remains a powerful platform for research in NREDs.<\/jats:p>","DOI":"10.3390\/ijms252111794","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T03:57:34Z","timestamp":1730692654000},"page":"11794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Decoding Nucleotide Repeat Expansion Diseases: Novel Insights from Drosophila melanogaster Studies"],"prefix":"10.3390","volume":"25","author":[{"given":"Sandra","family":"Atienzar-Aroca","sequence":"first","affiliation":[{"name":"Department of Dentristy, Faculty of Health Sciences, European University of Valencia, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marleen","family":"Kat","sequence":"additional","affiliation":[{"name":"Institute for Life Sciences and Chemistry, HU University of Applied Sciences Utrecht, NL-3584 Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1529-2635","authenticated-orcid":false,"given":"Arturo","family":"L\u00f3pez-Castel","sequence":"additional","affiliation":[{"name":"Human Translational Genomics Group, University Research Institute for Biotechnology and Biomedicine (BIOTECMED), Universidad de Valencia, 46100 Burjasot, Spain"},{"name":"INCLIVA Biomedical Research Institute, 46010 Valencia, Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liao, X., Zhu, W., Zhou, J., Li, H., Xu, X., Zhang, B., and Gao, X. 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