{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:40:12Z","timestamp":1788867612171,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research","award":["JP22H02793"],"award-info":[{"award-number":["JP22H02793"]}]},{"name":"Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research","award":["JP24K09982"],"award-info":[{"award-number":["JP24K09982"]}]},{"name":"Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research","award":["JP24tm0524001"],"award-info":[{"award-number":["JP24tm0524001"]}]},{"name":"Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research","award":["JP22nk0101641"],"award-info":[{"award-number":["JP22nk0101641"]}]},{"name":"Japan Agency for Medical Research and Development Program","award":["JP22H02793"],"award-info":[{"award-number":["JP22H02793"]}]},{"name":"Japan Agency for Medical Research and Development Program","award":["JP24K09982"],"award-info":[{"award-number":["JP24K09982"]}]},{"name":"Japan Agency for Medical Research and Development Program","award":["JP24tm0524001"],"award-info":[{"award-number":["JP24tm0524001"]}]},{"name":"Japan Agency for Medical Research and Development Program","award":["JP22nk0101641"],"award-info":[{"award-number":["JP22nk0101641"]}]},{"name":"HUSM Grant-in-Aid","award":["JP22H02793"],"award-info":[{"award-number":["JP22H02793"]}]},{"name":"HUSM Grant-in-Aid","award":["JP24K09982"],"award-info":[{"award-number":["JP24K09982"]}]},{"name":"HUSM Grant-in-Aid","award":["JP24tm0524001"],"award-info":[{"award-number":["JP24tm0524001"]}]},{"name":"HUSM Grant-in-Aid","award":["JP22nk0101641"],"award-info":[{"award-number":["JP22nk0101641"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background\/Objectives: UBL3 (Ubiquitin-like 3) is a protein that plays a crucial role in post-translational modifications, particularly in regulating protein transport within small extracellular vesicles. While previous research has predominantly focused on its interactions with \u03b1-synuclein, this study investigates UBL3\u2019s role in Huntington\u2019s disease (HD). HD is characterized by movement disorders and cognitive impairments, with its pathogenesis linked to toxic, polyglutamine (polyQ)-expanded mutant huntingtin fragments (mHTT). However, the mechanisms underlying the interaction between UBL3 and mHTT remain poorly understood. Methods: To elucidate this relationship, we performed hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) on postmortem brain tissue from HD patients. Gaussia princeps-based split-luciferase complementation assay and co-immunoprecipitation were employed to confirm the interaction between UBL3 and mHTT. Additionally, we conducted a HiBiT lytic detection assay to assess the influence of UBL3 on the intracellular sorting of mHTT. Finally, immunocytochemical staining was utilized to validate the colocalization and distribution of these proteins. Results: Our findings revealed UBL3-positive inclusions in the cytoplasm and nuclei of neurons throughout the striatum of HD patients. We discovered that UBL3 colocalizes and interacts with mHTT and modulates its intracellular sorting. Conclusions: These results suggest that UBL3 may play a significant role in the interaction and sorting of mHTT, contributing to the understanding of its potential implications in the pathophysiology of Huntington\u2019s disease.<\/jats:p>","DOI":"10.3390\/neurolint16060089","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T11:31:57Z","timestamp":1729596717000},"page":"1175-1188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["UBL3 Interacts with PolyQ-Expanded Huntingtin Fragments and Modifies Their Intracellular Sorting"],"prefix":"10.3390","volume":"16","author":[{"given":"Soho","family":"Oyama","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengsen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"},{"name":"Department of Neurosurgery, The Affiliated Hospital of Jiangnan University, Wuxi 214000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2055-3548","authenticated-orcid":false,"given":"Rafia","family":"Ferdous","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Tomochika","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"},{"name":"Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2062-0667","authenticated-orcid":false,"given":"Md. Shoriful","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-1823","authenticated-orcid":false,"given":"Md. Mahmudul","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6778-379X","authenticated-orcid":false,"given":"A. S. M.","family":"Waliullah","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashuang","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3286-0307","authenticated-orcid":false,"given":"Mst. Afsana","family":"Mimi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8889-2044","authenticated-orcid":false,"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Aramaki","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Takanashi","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2205-5665","authenticated-orcid":false,"given":"Tomoaki","family":"Kahyo","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"},{"name":"Quantum Imaging Laboratory, Division of Research and Development in Photonics Technology, Institute of Photonics Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Choju Medical Institute, Fukushimura Hospital, Yamanaka-19-14 Noyoricho, Toyohashi 441-8124, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-8105","authenticated-orcid":false,"given":"Daita","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Choju Medical Institute, Fukushimura Hospital, Yamanaka-19-14 Noyoricho, Toyohashi 441-8124, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1302-6467","authenticated-orcid":false,"given":"Mitsutoshi","family":"Setou","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"},{"name":"International Mass Imaging and Spatial Omics Center, Institute of Photonics Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27145","DOI":"10.1074\/jbc.M602283200","article-title":"MUBs, a Family of Ubiquitin-fold Proteins That Are Plasma Membrane-anchored by Prenylation","volume":"281","author":"Downes","year":"2006","journal-title":"J. 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