{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:03:41Z","timestamp":1753884221024,"version":"3.41.2"},"reference-count":42,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP23bm1423003","JP20be0704001"],"award-info":[{"award-number":["JP23bm1423003","JP20be0704001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["JP23H00420"],"award-info":[{"award-number":["JP23H00420"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"New Energy and Industrial Technology Development Organization"},{"DOI":"10.13039\/501100004823","name":"Nagoya University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004823","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by CAG trinucleotide expansion in the androgen receptor (AR) gene. To improve the quality of in vitro cell-based assays for the evaluation of potential drug candidates for SBMA, we developed a morphology-based phenotypic analysis for a muscle cell model of SBMA that involves multiparametric morphological profiling to quantitatively assess the therapeutic effects of drugs on muscle cell phenotype. The analysis was validated using dihydrotestosterone and pioglitazone, which have been shown to exacerbate and ameliorate the pathophysiology of SBMA, respectively. Gene expression analysis revealed activation of the JNK pathway in the SBMA cells compared to the control cells. Phenotypic analysis revealed the effect of naratriptan, a JNK inhibitor, on the phenotypic changes of SBMA cells, and the results were confirmed by LDH assays. We then trained a predictive machine learning model to classify the drug responses, and it successfully discriminated between pioglitazone-type and naratriptan-type morphological profiles based on their morphological characteristics. Our morphology-based phenotypic analysis provides a noninvasive and efficient screening method to accelerate the development of therapeutics for SBMA.<\/jats:p>","DOI":"10.1242\/dmm.052220","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T07:59:47Z","timestamp":1749196787000},"source":"Crossref","is-referenced-by-count":0,"title":["Label-free morphology-based phenotypic analysis of spinal and bulbar muscular atrophy muscle cell models"],"prefix":"10.1242","volume":"18","author":[{"given":"Kenji","family":"Sakakibara","sequence":"first","affiliation":[{"name":"Nagoya University Graduate School of Medicine, Tokai National Higher Education and Research System 1 Department of Neurology , , 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Nagoya 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Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550 ,","place":["Japan"]},{"name":"Nagoya University Institute for Advanced Research 3 , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Maeda","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine, Tokai National Higher Education and Research System 1 Department of Neurology , , 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-9407","authenticated-orcid":false,"given":"Ryuji","family":"Kato","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System 2 Department of Basic Medicinal Sciences , , Furocho, Chikusa-ku, Nagoya, Aichi 464-8601 ,","place":["Japan"]},{"name":"Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Tokai National Higher Education and Research System 4 , Furocho, Chikusa-ku, Nagoya, Aichi 464-8601 ,","place":["Japan"]},{"name":"Institute for Glyco-core Research (iGCORE), Tokai National Higher Education and Research System 5 , Furocho, Chikusa-ku, Nagoya, Aichi 464-8601 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-9311","authenticated-orcid":false,"given":"Masahisa","family":"Katsuno","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine, Tokai National Higher Education and Research System 1 Department of Neurology , , 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550 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