{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:16:49Z","timestamp":1790691409080,"version":"4.1.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI grant numbers 23590642"],"award-info":[{"award-number":["KAKENHI grant numbers 23590642"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI grant numbers 26460221"],"award-info":[{"award-number":["KAKENHI grant numbers 26460221"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI grant numbers 26460629"],"award-info":[{"award-number":["KAKENHI grant numbers 26460629"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI grant numbers 17H04010"],"award-info":[{"award-number":["KAKENHI grant numbers 17H04010"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI grant numbers 20K07066"],"award-info":[{"award-number":["KAKENHI grant numbers 20K07066"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["Research on Development of New Drugs (Project ID: 167698659)"],"award-info":[{"award-number":["Research on Development of New Drugs (Project ID: 167698659)"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HIGO Program Research Funding Project","award":["(Fiscal Years 2019 and 2020)"],"award-info":[{"award-number":["(Fiscal Years 2019 and 2020)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann\u2013Pick disease type C (NPC) is a recessive hereditary disease caused by mutation of the NPC1 or NPC2 gene. It is characterized by abnormality of cellular cholesterol trafficking with severe neuronal and hepatic injury. In this study, we investigated the potential of glycoprotein nonmetastatic melanoma protein B (GPNMB) to act as a biomarker reflecting the therapeutic effect of 2-hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) in an NPC mouse model. We measured serum, brain, and liver expression levels of GPNMB, and evaluated their therapeutic effects on NPC manifestations in the brain and liver after the intracerebroventricular administration of HP-\u03b2-CD in Npc1 gene-deficient (Npc1\u2212\/\u2212) mice. Intracerebroventricular HP-\u03b2-CD inhibited cerebellar Purkinje cell damage in Npc1\u2212\/\u2212 mice and significantly reduced serum and cerebellar GPNMB levels. Interestingly, we also observed that the intracerebral administration significantly reduced hepatic GPNMB expression and elevated serum ALT in Npc1\u2212\/\u2212 mice. Repeated doses of intracerebroventricular HP-\u03b2-CD (30 mg\/kg, started at 4 weeks of age and repeated every 2 weeks) drastically extended the lifespan of Npc1\u2212\/\u2212 mice compared with saline treatment. In summary, our results suggest that GPNMB level in serum is a potential biomarker for evaluating the attenuation of NPC pathophysiology by intracerebroventricular HP-\u03b2-CD treatment.<\/jats:p>","DOI":"10.3390\/ijms22010452","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T10:35:12Z","timestamp":1609842912000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Intracerebroventricular Treatment with 2-Hydroxypropyl-\u03b2-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann\u2013Pick Disease Type C Model Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Madoka","family":"Fukaura","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"},{"name":"Program for Leading Graduate Schools \u201cHIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program,\u201d Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9442-4469","authenticated-orcid":false,"given":"Yoichi","family":"Ishitsuka","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ushihama","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusei","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1456-7721","authenticated-orcid":false,"given":"Yuki","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Takeo","sequence":"additional","affiliation":[{"name":"Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Nakagata","sequence":"additional","affiliation":[{"name":"Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9315-8282","authenticated-orcid":false,"given":"Keiichi","family":"Motoyama","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taishi","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Arima","sequence":"additional","affiliation":[{"name":"Laboratory of Evidence-based Pharmacotherapy, Daiichi University of Pharmacy, 22-1 Tamagawa-machi, Minami-ku, Fukuoka 815-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kurauchi","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9894-4768","authenticated-orcid":false,"given":"Takahiro","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Katsuki","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Higaki","sequence":"additional","affiliation":[{"name":"Research Initiative Center, Organization for Research Initiative and Promotion, Tottori University, 86 Nishi-cho, Yonago 683-8503, 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