{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:12:53Z","timestamp":1772118773950,"version":"3.50.1"},"reference-count":94,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011415","name":"Office of the Vice President for Research, Wayne State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS086778"],"award-info":[{"award-number":["R01NS086778"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS0867778\u201010A1S1"],"award-info":[{"award-number":["R01NS0867778\u201010A1S1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dentatorubral\u2010Pallidoluysian Atrophy (DRPLA) is a dominant neurodegenerative disease caused by CAG triplet repeat expansion in\n                    <jats:italic>ATN1<\/jats:italic>\n                    , which encodes the transcriptional co\u2010repressor Atrophin\u20101. DRPLA features motor, cognitive, and epileptic symptoms and shares pathogenic mechanisms with other polyglutamine (polyQ) disorders, including protein misfolding, impaired autophagy, and transcriptional dysregulation. To understand disease mechanisms, we performed RNA\u2010seq on HEK293T cells stably over\u2010expressing wild\u2010type or pathogenic ATN1. Cells expressing pathogenic ATN1 exhibited a distinct transcriptomic profile, including disruptions in synaptic organization, extracellular matrix remodeling, ion channel expression, and neurotransmission. Several genes tied to neurodevelopmental, neurodegenerative, and oncogenic pathways were fully activated or silenced. Dysregulated pathways also included inflammation, chromatin remodeling, stress responses, and redox imbalance. Heat shock protein expression changes suggested proteotoxic stress and impaired protein quality control, with some findings conserved in a previously reported\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    <\/jats:styled-content>\n                    model of DRPLA. The transcriptomic signatures that we describe here expand understanding of the normal functions of ATN1 and the biology of disease of DRPLA.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70089","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T07:29:15Z","timestamp":1765178955000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disrupted Transcriptional Networks in Mammalian Cells Stably Over\u2010Expressing Pathogenic Atrophin\u20101"],"prefix":"10.1002","volume":"103","author":[{"given":"Oluwademilade","family":"Nuga","sequence":"first","affiliation":[{"name":"Department of Pharmacology Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masoumeh","family":"Pourhadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia P.","family":"Rausch","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4399-5549","authenticated-orcid":false,"given":"Sokol V.","family":"Todi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wayne State University School of Medicine  Detroit Michigan USA"},{"name":"Department of Neurology Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr500196b"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JHD\u2010200421"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2019.101551"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2023.120828"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2012.11.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adn4600"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.7916\/D81N9HST"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201014\u2010128"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa212"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96765"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8730"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.10.010"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz115"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.11.010"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","unstructured":"Huang H. T. L.Charron M.Fu et\u00a0al.2025.\u201cResilience to Endoplasmic Reticulum Stress Mitigates Calcium\u2010Dependent Membrane Hyperexcitability Underlying Late Disease Onset in SCA6.\u201dbioRxiv.https:\/\/doi.org\/10.1101\/2025.01.27.635103.","DOI":"10.1101\/2025.01.27.635103"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.182"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/357027"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11010162"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.08.023"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071223"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60742"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.974167"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(16)00099\u20105"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0194\u20109"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2019.101512"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201200364"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705211200"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06909"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010023\u201000549\u20100"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathmechdis\u2010012418\u2010012857"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11172632"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010024\u201009008\u2010z"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.46.29238"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.08.025"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.225151.113"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16010"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(17)30161\u20108"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1086\/521275"},{"key":"e_1_2_10_41_1","doi-asserted-by":"crossref","unstructured":"Naama N. A. C.Konrad S.Sherif et\u00a0al.2025. \u201cMitochondrial Dysfunction Precedes Neurodegeneration in DRPLA Patient\u2010Derived Neurons and Phenylbutyrate Improves Survival.\u201dbioRxiv.https:\/\/doi.org\/10.1101\/2025.09.02.673807.","DOI":"10.1101\/2025.09.02.673807"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094\u2010177"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.1"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1705"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.31"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29355"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211224200"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg168"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkad180"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410408"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002018"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1112688"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2025.106834"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2021.05.001"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2024.04.001"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.25278"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161596"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007972\u20102"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl182"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.6.997"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn403"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.99"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896\u20106273(00)80839\u20109"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.267"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.201"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610274200"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010008\u20108403\u20109"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20190966"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2005.07.015"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084209"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010015\u20109452\u20103"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg766"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405130200"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20075"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409984200"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.05.065"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201065172\u20104"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20104658.2010.07893.x"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.642773"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.796991"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.10.039"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2004.08.014"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdab179"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1621\/nrs.06009"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S68773"},{"key":"e_1_2_10_86_1","volume-title":"GeneReviews((R))","author":"Whitton C.","year":"1993"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.5.939"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:23:1\u20102:069"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102009\u201010\u20107\u2010r74"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511677200"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1159\/000331233"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311\u2010024\u201001722\u2010w"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(01)00630\u20104"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00908"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033019"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.70089","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T08:47:12Z","timestamp":1766738832000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.70089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":94,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jnr.70089"],"URL":"https:\/\/doi.org\/10.1002\/jnr.70089","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JNR.70089\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70089\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70089\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70089\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70089\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70089\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70089\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70089\/v1\/review1","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70089"}}