{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:46:56Z","timestamp":1790293616143,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001869","name":"Academia Sinica","doi-asserted-by":"publisher","award":["AS\u2010IA\u2010108\u2010L06"],"award-info":[{"award-number":["AS\u2010IA\u2010108\u2010L06"]}],"id":[{"id":"10.13039\/501100001869","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Huntington's disease (HD) is a neurodegenerative disease caused by CAG\u2010repeat expansions (&gt;36) in exon 1 of <jats:italic>HTT,<\/jats:italic> which dysregulates multiple cellular machineries. Translin\u2010associated protein X (TRAX) is a scaffold protein with diverse functions, including suppressing the microRNA (miRNA)\u2010mediated silencing by degrading pre\u2010miRNA. To date, the role of TRAX in neurodegenerative diseases remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We delineated the role of TRAX upregulation during HD progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of TRAX in the brains of humans and three mouse models with HD were analyzed by immunohistochemistry staining, western blot, and quantitative reverse transcription\u2010polymerase chain reaction. Adeno\u2010associated viruses harboring TRAX short hairpin RNA were intrastriatally injected into HD mice to downregulate TRAX. HD\u2010like symptoms were analyzed by behavioral and biochemical assessments. The miRNA\u2010sequencing and RNA\u2010sequencing analyses were used to identify the TRAX\u2010 regulated miRNA\u2010messenger RNA (mRNA) axis during HD progression. The identified gene targets were validated biochemically in mouse and human striatal cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We discovered that TRAX was upregulated in the brains of HD patients and three HD mouse models. Downregulation of TRAX enhanced 83 miRNAs (including miR\u2010330\u20103p, miR\u2010496a\u20103p) and subsequently changed the corresponding mRNA networks critical for HD pathogenesis (eg, DARPP\u201032 and brain\u2010derived neurotrophic factor). Disruption of the TRAX\u2010mediated miRNA\u2010mRNA axis accelerated the progression of HD\u2010like symptoms, including the degeneration of motor function, accumulation of mHTT aggregates, and shortened neurite outgrowth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated that TRAX upregulation is authentic and protective in HD. Our study provides a novel layer of regulation for HD pathogenesis and may lead to the development of new therapeutic strategies for HD. \u00a9 2022 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29174","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T08:06:07Z","timestamp":1661241967000},"page":"2008-2020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>TRAX<\/scp> Provides Neuroprotection for Huntington's Disease Via Modulating a Novel Subset of <scp>MicroRNAs<\/scp>"],"prefix":"10.1002","volume":"37","author":[{"given":"Yu\u2010Ting","family":"Weng","sequence":"first","affiliation":[{"name":"Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica  Taipei Taiwan"},{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei 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