{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T10:15:05Z","timestamp":1772619305303,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japan Society for the Promotion of Science","award":["JSPS KAKENHI grant number 23590642, 26460221, and 17H04010"],"award-info":[{"award-number":["JSPS KAKENHI grant number 23590642, 26460221, and 17H04010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann\u2013Pick disease type C (NPC) is an autosomal recessive disorder characterized by abnormal accumulation of free cholesterol and sphingolipids in lysosomes. The iminosugar miglustat, which inhibits hexosylceramide synthesis, is used for NPC treatment, and 2-hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD), a cyclic oligosaccharide derivative, is being developed to treat NPC. Moreover, therapeutic potential of 2-hydroxypropyl-\u03b3-cyclodextrin (HP-\u03b3-CD) was shown in NPC models, although its mechanism of action remains unclear. Here, we investigated the effects of HP-\u03b2-CD, HP-\u03b3-CD, and their homolog 2-hydroxypropyl-\u03b1-cyclodextrin (HP-\u03b1-CD) on lipid accumulation in Npc1-null Chinese hamster ovary (CHO) cells compared with those of miglustat. HP-\u03b2-CD and HP-\u03b3-CD, unlike HP-\u03b1-CD, reduced intracellular free cholesterol levels and normalized the lysosome changes in Npc1-null cells but not in wild-type CHO cells. In contrast, miglustat did not normalize intracellular free cholesterol accumulation or lysosome changes in Npc1-null cells. However, miglustat decreased the levels of hexosylceramide and tended to increase those of sphingomyelins in line with its action as a glucosylceramide synthase inhibitor in both Npc1-null and wild-type CHO cells. Interestingly, HP-\u03b2-CD and HP-\u03b3-CD, unlike HP-\u03b1-CD, reduced sphingomyelins in Npc1-null, but not wild-type, cells. In conclusion, HP-\u03b2-CD and HP-\u03b3-CD reduce the accumulation of sphingolipids, mainly sphingomyelins, and free cholesterol as well as lysosome changes in Npc1-null, but not in wild-type, CHO cells.<\/jats:p>","DOI":"10.3390\/ijms21030898","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T01:25:51Z","timestamp":1580693151000},"page":"898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Differential Effects of 2-Hydroxypropyl-Cyclodextrins on Lipid Accumulation in Npc1-Null Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Sanzana","family":"Hoque","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nodoka","family":"Sakata","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madoka","family":"Fukaura","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"},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taishi","family":"Higashi","sequence":"additional","affiliation":[{"name":"Priority Organization for Innovation and Excellence, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaki","family":"Komiya","sequence":"additional","affiliation":[{"name":"Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsumi","family":"Irie","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"},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C","volume":"5","author":"Vanier","year":"2010","journal-title":"Orphanet J. 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