{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:17:22Z","timestamp":1787987842315,"version":"build-2784847793"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Allianz Pharmascience Limited (Taipei, Taiwan) through collaboration with Changhua Christian Hospital","award":["108-CCH-Allianz-001"],"award-info":[{"award-number":["108-CCH-Allianz-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Unlike other nuclear factor erythroid-2-related factor 2 (Nrf2) activators, the mechanism of action of curcumin analog, ASC-JM17 (JM17), in regulating oxidative homeostasis remains unknown. Spinocerebellar ataxia type 3 (SCA3) is an inherited polyglutamine neurodegenerative disease caused mainly by polyglutamine neurotoxicity and oxidative stress. Presently, we compared actions of JM17 with those of known Nrf2 activators, omaveloxolone (RTA-408) and dimethyl fumarate (DMF), using human neuroblastoma SK-N-SH cells with stable transfection of full-length ataxin-3 protein with 78 CAG repeats (MJD78) to clarify the resulting pathological mechanism by assaying mitochondrial function, mutant ataxin-3 protein toxicity, and oxidative stress. JM17, 1 \u03bcM, comprehensively restored mitochondrial function, decreased mutant protein aggregates, and attenuated intracellular\/mitochondrial reactive oxygen species (ROS) levels. Although JM17 induced dose-dependent Nrf2 activation, a low dose of JM17 (less than 5 \u03bcM) still had a better antioxidant ability compared to the other Nrf2 activators and specifically increased mitochondrial superoxide dismutase 2 in an Nrf2-dependent manner as shown by knockdown experiments with siRNA. It showed that activation of Nrf2 in response to ROS generated in mitochondria could play an import role in the benefit of JM17. This study presents the diversified regulation of JM17 in a pathological process and helped develop more effective therapeutic strategies for SCA3.<\/jats:p>","DOI":"10.3390\/antiox11071389","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:19:21Z","timestamp":1658189961000},"page":"1389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["In Vitro Efficacy and Molecular Mechanism of Curcumin Analog in Pathological Regulation of Spinocerebellar Ataxia Type 3"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0028-0183","authenticated-orcid":false,"given":"Yu-Ling","family":"Wu","sequence":"first","affiliation":[{"name":"Vascular and Genomic Center, Institute of ATP, Changhua Christian Hospital, Changhua 50091, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Changhua Christian Hospital, Changhua 50091, Taiwan"},{"name":"General Research Laboratory of Research Department, Changhua Christian Hospital, Changhua 50091, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chun","family":"Chao","sequence":"additional","affiliation":[{"name":"Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua 50091, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardy","family":"Chan","sequence":"additional","affiliation":[{"name":"Allianz Pharmascience Limited, Taipei 10682, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Life Science, Life Science Research Center, Tunghai University, Taichung 40704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-San","family":"Liu","sequence":"additional","affiliation":[{"name":"Vascular and Genomic Center, Institute of ATP, Changhua Christian Hospital, Changhua 50091, Taiwan"},{"name":"Department of Neurology, Changhua Christian Hospital, Changhua 50094, Taiwan"},{"name":"Graduate Institute of Integrated Medicine College of Chinese Medicine, China Medical University, Taichung 40447, Taiwan"},{"name":"Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/ana.410390411","article-title":"Spinocerebellar ataxia 3 and Machado-Joseph disease: Clinical, molecular, and neuropathological features","volume":"39","author":"Durr","year":"1996","journal-title":"Ann. 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