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Understanding and Treating Niemann–Pick Type C Disease: Models Matter
Article

Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice

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Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
2
Program for Leading Graduate Schools “HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program,” Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
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Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Laboratory of Evidence-based Pharmacotherapy, Daiichi University of Pharmacy, 22-1 Tamagawa-machi, Minami-ku, Fukuoka 815-8511, Japan
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Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Research Initiative Center, Organization for Research Initiative and Promotion, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan
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Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(1), 452; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010452
Received: 8 December 2020 / Revised: 30 December 2020 / Accepted: 30 December 2020 / Published: 5 January 2021
Niemann–Pick 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-β-cyclodextrin (HP-β-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-β-CD in Npc1 gene-deficient (Npc1−/−) mice. Intracerebroventricular HP-β-CD inhibited cerebellar Purkinje cell damage in Npc1−/− 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−/− mice. Repeated doses of intracerebroventricular HP-β-CD (30 mg/kg, started at 4 weeks of age and repeated every 2 weeks) drastically extended the lifespan of Npc1−/− 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-β-CD treatment. View Full-Text
Keywords: Niemann–Pick disease type C; 2-hydroxypropyl-β-cyclodextrin; glycoprotein nonmetastatic melanoma B Niemann–Pick disease type C; 2-hydroxypropyl-β-cyclodextrin; glycoprotein nonmetastatic melanoma B
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MDPI and ACS Style

Fukaura, M.; Ishitsuka, Y.; Shirakawa, S.; Ushihama, N.; Yamada, Y.; Kondo, Y.; Takeo, T.; Nakagata, N.; Motoyama, K.; Higashi, T.; Arima, H.; Kurauchi, Y.; Seki, T.; Katsuki, H.; Higaki, K.; Matsuo, M.; Irie, T. Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice. Int. J. Mol. Sci. 2021, 22, 452. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010452

AMA Style

Fukaura M, Ishitsuka Y, Shirakawa S, Ushihama N, Yamada Y, Kondo Y, Takeo T, Nakagata N, Motoyama K, Higashi T, Arima H, Kurauchi Y, Seki T, Katsuki H, Higaki K, Matsuo M, Irie T. Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice. International Journal of Molecular Sciences. 2021; 22(1):452. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010452

Chicago/Turabian Style

Fukaura, Madoka, Yoichi Ishitsuka, Seiichi Shirakawa, Naoki Ushihama, Yusei Yamada, Yuki Kondo, Toru Takeo, Naomi Nakagata, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Yuki Kurauchi, Takahiro Seki, Hiroshi Katsuki, Katsumi Higaki, Muneaki Matsuo, and Tetsumi Irie. 2021. "Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice" International Journal of Molecular Sciences 22, no. 1: 452. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010452

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