{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:21:12Z","timestamp":1790749272889,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","award":["CSH-2018-C-003"],"award-info":[{"award-number":["CSH-2018-C-003"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["108-2320-B-040-029-MY2, 108-2314-B-040-023-MY3, 109-2320-B-040-021"],"award-info":[{"award-number":["108-2320-B-040-029-MY2, 108-2314-B-040-023-MY3, 109-2320-B-040-021"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the bilateral project from National Chung Hsing University and Chung Shan Medical University","award":["NCHU-CSMU-10901"],"award-info":[{"award-number":["NCHU-CSMU-10901"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is an autosomal-dominant brain disorder caused by mutant huntingtin (mHtt). Although the detailed mechanisms remain unclear, the mutational expansion of polyglutamine in mHtt is proposed to induce protein aggregates and neuronal toxicity. Previous studies have shown that the decreased insulin sensitivity is closely related to mHtt-associated impairments in HD patients. However, how mHtt interferes with insulin signaling in neurons is still unknown. In the present study, we used a HD cell model to demonstrate that the miR-302 cluster, an embryonic stem cell-specific polycistronic miRNA, is significantly downregulated in mHtt-Q74-overexpressing neuronal cells. On the contrary, restoration of miR-302 cluster was shown to attenuate mHtt-induced cytotoxicity by improving insulin sensitivity, leading to a reduction of mHtt aggregates through the enhancement of autophagy. In addition, miR-302 also promoted mitophagy and stimulated Sirt1\/AMPK-PGC1\u03b1 pathway thereby preserving mitochondrial function. Taken together, these results highlight the potential role of miR-302 cluster in neuronal cells, and provide a novel mechanism for mHtt-impaired insulin signaling in the pathogenesis of HD.<\/jats:p>","DOI":"10.3390\/ijms22168424","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T09:35:32Z","timestamp":1628156132000},"page":"8424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["miR-302 Attenuates Mutant Huntingtin-Induced Cytotoxicity through Restoration of Autophagy and Insulin Sensitivity"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-9152","authenticated-orcid":false,"given":"Ching-Chi","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Chung Shan Medical University Hospital, Taichung 402, Taiwan"},{"name":"School of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-028X","authenticated-orcid":false,"given":"Sing-Hua","family":"Tsou","sequence":"additional","affiliation":[{"name":"Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3729-989X","authenticated-orcid":false,"given":"Wei-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Jui","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Psychology, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-1822","authenticated-orcid":false,"given":"Hui-Chih","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Yaw","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0022-6240","authenticated-orcid":false,"given":"Sandeep Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Indian Scientific Education and Technology Foundation, Lucknow 226002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"General Education Center, National Taiwan University of Sport, Taichung 404, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4553-3727","authenticated-orcid":false,"given":"Chih-Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.arr.2018.11.006","article-title":"Targeting the proteostasis network in Huntington\u2019s disease","volume":"49","author":"Soares","year":"2019","journal-title":"Ageing Res. 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