{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:58:13Z","timestamp":1777579093530,"version":"3.51.4"},"reference-count":183,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-029255 (PTDC\/MED-GEN\/29255\/2017)"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029255 (PTDC\/MED-GEN\/29255\/2017)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The number of neurodegenerative diseases resulting from repeat expansion has increased extraordinarily in recent years. In several of these pathologies, the repeat can be transcribed in RNA from both DNA strands producing, at least, one toxic RNA repeat that causes neurodegeneration by a complex mechanism. Recently, seven diseases have been found caused by a novel intronic pentanucleotide repeat in distinct genes encoding proteins highly expressed in the cerebellum. These disorders are clinically heterogeneous being characterized by impaired motor function, resulting from ataxia or epilepsy. The role that apparently normal proteins from these mutant genes play in these pathologies is not known. However, recent advances in previously known spinocerebellar ataxias originated by abnormal non-coding pentanucleotide repeats point to a gain of a toxic function by the pathogenic repeat-containing RNA that abnormally forms nuclear foci with RNA-binding proteins. In cells, RNA foci have been shown to be formed by phase separation. Moreover, the field of repeat expansions has lately achieved an extraordinary progress with the discovery that RNA repeats, polyglutamine, and polyalanine proteins are crucial for the formation of nuclear membraneless organelles by phase separation, which is perturbed when they are expanded. This review will cover the amazing advances on repeat diseases.<\/jats:p>","DOI":"10.3390\/cells11020205","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T20:29:26Z","timestamp":1641760166000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Molecular Mechanisms in Pentanucleotide Repeat Diseases"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3890-852X","authenticated-orcid":false,"given":"Joana R.","family":"Loureiro","sequence":"first","affiliation":[{"name":"Genetics of Cognitive Dysfunction Laboratory, i3S- Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Molecular and Cell Biology, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Ana F.","family":"Castro","sequence":"additional","affiliation":[{"name":"Genetics of Cognitive Dysfunction Laboratory, i3S- Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Molecular and Cell Biology, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Ana S.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Genetics of Cognitive Dysfunction Laboratory, i3S- Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Molecular and Cell Biology, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2610-5260","authenticated-orcid":false,"given":"Isabel","family":"Silveira","sequence":"additional","affiliation":[{"name":"Genetics of Cognitive Dysfunction Laboratory, i3S- Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Molecular and Cell Biology, Universidade do Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41580-021-00396-0","article-title":"Author Correction: Molecular mechanisms underlying nucleotide repeat expansion disorders","volume":"22","author":"Malik","year":"2021","journal-title":"Nat. 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