286090 20260413125809.0 10.1016/j.celrep.2026.117146 doi pmid:41871099 pmid 2211-1247 ISSN 2639-1856 ISSN DZNE-2026-00386 English 610 Loureiro, Joana R P:(DE-HGF)0 0 First author The insertion of an ATTTC repeat in an Alu element hyperactivates a neurodevelopmental enhancer in spinocerebellar ataxia type 37. Maryland Heights, MO 2026 Cell Press article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1776077756_32196 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Alu elements are evolutionarily very old primate-specific interspersed repeat elements that constitute ∼11% of the human genome. They are a source of short tandem repeats (STRs), which often expand in size and cause inherited neuromuscular and neurodegenerative disorders. How expanded STR insertion mutations within Alu STRs culminate in disease remains unknown. Here, we report an Alu STR located in an intron of DAB1 that functions as a neurodevelopmental enhancer. We demonstrate that an ATTTC repeat insertion in this DAB1 Alu STR, known to cause spinocerebellar ataxia type 37 (SCA37), hyperactivates a neurodevelopmental DAB1 enhancer. Importantly, we show that neurons derived from SCA37 subjects have higher levels of DAB1 expression and that DAB1 overexpression causes abnormal axonal pathfinding in vivo. Overall, these results establish that neuronal dysregulation of a developmental DAB1 Alu STR enhancer contributes to SCA37 pathogenesis, an unexplored mechanism likely acting in many Alu STR diseases, potentially reshaping the therapeutic landscape. 354 - Disease Prevention and Healthy Aging (POF4-354) G:(DE-HGF)POF4-354 POF4-354 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 4C-seq Other CAGE Other CP: genomics Other CP: neuroscience Other DAB1 primate-specific Alu element Other SCA37 Other STR Other axonal pathfinding Other cap analysis of gene expression Other cerebellar transcriptional enhancer Other circularized chromosome conformation capture sequencing Other iPSN Other neurodegenerative disease Other pentanucleotide repeat expansion Other short tandem repeat Other spinocerebellar ataxia type 37 Other Castro, Ana F 1 Figueiredo, Ana S 2 Eufrásio, Ana 3 Dhingra, Ashutosh P:(DE-2719)2811729 4 dzne Galhardo, Mafalda 5 Marcelino, Hugo 6 Rodrigues, Catarina C 7 Sampaio, Paula 8 Azevedo, Maria 9 Sousa, Mafalda 10 Dória, Sofia 11 Rizzu, Patrizia P:(DE-2719)2810718 12 Heutink, Peter P:(DE-2719)2810728 13 Bessa, José 14 Silveira, Isabel 15 10.1016/j.celrep.2026.117146 Vol. 45, no. 4, p. 117146 - PERI:(DE-600)2649101-1 4 117146 Cell reports 45 2026 2211-1247 http://pub.dzne.de/record/286090/files/DZNE-2026-00386.pdf Restricted http://pub.dzne.de/record/286090/files/DZNE-2026-00386.pdf?subformat=pdfa pdfa Restricted Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-HGF)0 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2811729 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 12 P:(DE-2719)2810718 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 13 P:(DE-2719)2810728 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-354 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Prevention and Healthy Aging 0 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2025-11-10 JCR StatID:(DE-HGF)0100 StatID CELL REP : 2022 2025-11-10 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2025-11-10 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2025-08-21T14:50:29Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2025-08-21T14:50:29Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2025-08-21T14:50:29Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2025-11-10 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2025-11-10 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2025-11-10 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2025-11-10 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2025-11-10 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2025-11-10 IF >= 5 StatID:(DE-HGF)9905 StatID CELL REP : 2022 2025-11-10 Article Processing Charges StatID:(DE-HGF)0561 StatID 2025-11-10 Fees StatID:(DE-HGF)0700 StatID 2025-11-10 I:(DE-2719)1210002 AG Heutink Genome Biology of Neurodegenerative Diseases 0 I:(DE-2719)1210009 AG Rizzu Applied Genomics for Neurodegenerative Diseases 1 journal EDITORS VDBINPRINT I:(DE-2719)1210002 I:(DE-2719)1210009 UNRESTRICTED