{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:18:12Z","timestamp":1791919092332,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T00:00:00Z","timestamp":1475020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000097","name":"NIH National Center for Research Resources","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"NIH National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["1UL1TR001079"],"award-info":[{"award-number":["1UL1TR001079"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"NIH National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["NS064138"],"award-info":[{"award-number":["NS064138"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by a CAG repeat expansion in the gene ataxin\u20102 (\n                      <jats:italic>ATXN2<\/jats:italic>\n                      ).\n                      <jats:italic>ATXN2<\/jats:italic>\n                      intermediate\u2010length CAG expansions were identified as a risk factor for amyotrophic lateral sclerosis (ALS). The\n                      <jats:italic>ATXN2<\/jats:italic>\n                      CAG repeat is translated into polyglutamine, and SCA2 pathogenesis has been thought to derive from ATXN2 protein containing an expanded polyglutamine tract. However, recent evidence of bidirectional transcription at multiple CAG\/CTG disease loci has led us to test whether additional mechanisms of pathogenesis may contribute to SCA2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this work, using human postmortem tissue, various cell models, and animal models, we provide the first evidence that an antisense transcript at the SCA2 locus contributes to SCA2 pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrate the expression of a transcript, containing the repeat as a CUG tract, derived from a gene (\n                      <jats:italic>ATXN2\u2010AS<\/jats:italic>\n                      ) directly antisense to\n                      <jats:italic>ATXN2. ATXN2\u2010AS<\/jats:italic>\n                      transcripts with normal and expanded CUG repeats are expressed in human postmortem SCA2 brains, human SCA2 fibroblasts, induced SCA2 pluripotent stem cells, SCA2 neural stem cells, and lymphoblastoid lines containing an expanded\n                      <jats:italic>ATXN2<\/jats:italic>\n                      allele associated with ALS.\n                      <jats:italic>ATXN2\u2010AS<\/jats:italic>\n                      transcripts with a CUG repeat expansion are toxic in an SCA2 cell model and form RNA foci in SCA2 cerebellar Purkinje cells. Finally, we detected missplicing of amyloid beta precursor protein and N\u2010methyl\u2010D\u2010aspartate receptor 1 in SCA2 brains, consistent with findings in other diseases characterized by RNA\u2010mediated pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      These results suggest that\n                      <jats:italic>ATXN2\u2010AS<\/jats:italic>\n                      has a role in SCA2 and possibly ALS pathogenesis, and may therefore provide a novel therapeutic target for these diseases. Ann Neurol 2016;80:600\u2013615\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24761","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T04:32:48Z","timestamp":1471408368000},"page":"600-615","source":"Crossref","is-referenced-by-count":70,"title":["<scp>\n                      <i>ATXN2\u2010AS<\/i>\n                    <\/scp>\n                    , a gene antisense to\n                    <scp>\n                      <i>ATXN2<\/i>\n                    <\/scp>\n                    , is associated with spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"80","author":[{"given":"Pan P.","family":"Li","sequence":"first","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Research and Neurology Services, Veterans Affairs Medical Center Albany NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangbin","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, and McKnight Brain Institute University of Florida Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Arbez","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharan","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Benjamin","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Molecular Neuroscience Hong Kong University of Science and Technology, Clear Water Bay Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Program of Cellular and Molecular Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnulf H.","family":"Koeppen","sequence":"additional","affiliation":[{"name":"Research and Neurology Services, Veterans Affairs Medical Center Albany NY"},{"name":"Department of Neurology and Pathology Albany Medical College Albany NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell L.","family":"Margolis","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Program of Cellular and Molecular Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Pulst","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Utah Salt Lake City 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