{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:32:33Z","timestamp":1762522353508,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T00:00:00Z","timestamp":1574208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type II (MPS II) is a rare lysosomal storage disease (LSD) involving a genetic error in iduronic acid-2-sulfatase (IDS) metabolism that leads to accumulation of glycosaminoglycans within intracellular lysosomes. The primary treatment for MPS II, enzyme replacement therapy, is not effective for central nervous system (CNS) symptoms, such as intellectual disability, because the drugs do not cross the blood\u2013brain barrier. Recently, autophagy has been associated with LSDs. In this study, we examined the morphologic relationship between neuronal damage and autophagy in IDS knockout mice using antibodies against subunit c of mitochondrial adenosine triphosphate (ATP) synthetase and p62. Immunohistological changes suggesting autophagy, such as vacuolation, were observed in neurons, microglia, and pericytes throughout the CNS, and the numbers increased over postnatal development. Oral administration of chloroquine, which inhibits autophagy, did not suppress damage to microglia and pericytes, but greatly reduced neuronal vacuolation and eliminated neuronal cells with abnormal inclusions. Thus, decreasing autophagy appears to prevent neuronal degeneration. These results suggest that an autophagy modulator could be used in addition to conventional enzyme replacement therapy to preserve the CNS in patients with MPS II.<\/jats:p>","DOI":"10.3390\/ijms20235829","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T11:06:03Z","timestamp":1574247963000},"page":"5829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Autophagy in the Central Nervous System and Effects of Chloroquine in Mucopolysaccharidosis Type II Mice"],"prefix":"10.3390","volume":"20","author":[{"given":"Mitsuyo","family":"Maeda","sequence":"first","affiliation":[{"name":"Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Hyogo 650-0047, Japan"},{"name":"Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Hyogo 650-0047, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Seto","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan"},{"name":"Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiho","family":"Kadono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideto","family":"Morimoto","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals Co., Ltd., Hyogo 659-0021, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiho","family":"Kida","sequence":"additional","affiliation":[{"name":"JCR Pharmaceuticals Co., Ltd., Hyogo 659-0021, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuo","family":"Suga","sequence":"additional","affiliation":[{"name":"Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Hyogo 650-0047, Japan"},{"name":"Japan Electron Optics Laboratory (JEOL) Ltd., Tokyo 196-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motohiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Hyogo 650-0047, Japan"},{"name":"Japan Electron Optics Laboratory (JEOL) Ltd., Tokyo 196-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosky","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Hyogo 650-0047, Japan"},{"name":"Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Hyogo 650-0047, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Hamazaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Shintaku","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13023-017-0662-9","article-title":"Open issues in Mucopolysaccharidosis type I-Hurler","volume":"12","author":"Parini","year":"2017","journal-title":"Orphanet. 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