{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:53:28Z","timestamp":1790679208073,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T00:00:00Z","timestamp":1629504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FONDEQUIP","award":["EQM150093"],"award-info":[{"award-number":["EQM150093"]}]},{"name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica-Chile","award":["AFB170005"],"award-info":[{"award-number":["AFB170005"]}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1161065"],"award-info":[{"award-number":["1161065"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1201668"],"award-info":[{"award-number":["1201668"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1180337"],"award-info":[{"award-number":["1180337"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1190334"],"award-info":[{"award-number":["1190334"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Niemann-Pick type C disease (NPCD) is a lysosomal storage disorder caused by mutations in the NPC1 gene. The most affected tissues are the central nervous system and liver, and while significant efforts have been made to understand its neurological component, the pathophysiology of the liver damage remains unclear. In this study, hepatocytes derived from wild type and Npc1\u2212\/\u2212 mice were analyzed by mass spectrometry (MS)-based proteomics in conjunction with bioinformatic analysis. We identified 3832 proteins: 416 proteins had a p-value smaller than 0.05, of which 37% (n = 155) were considered differentially expressed proteins (DEPs), 149 of them were considered upregulated, and 6 were considered downregulated. We focused the analysis on pathways related to NPC pathogenic mechanisms, finding that the most significant changes in expression levels occur in proteins that function in the pathways of liver damage, lipid metabolism, and inflammation. Moreover, in the group of DEPs, 30% (n = 47) were identified as lysosomal proteins and 7% (n = 10) were identified as mitochondrial proteins. Importantly, we found that lysosomal DEPs, including CTSB\/D\/Z, LIPA, DPP7 and GLMP, and mitocondrial DEPs, AKR1B10, and VAT1 had been connected with liver fibrosis, damage, and steatosis in previous studies, validiting our dataset. Our study found potential therapeutic targets for the treatment of liver damage in NPCD.<\/jats:p>","DOI":"10.3390\/cells10082159","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T21:42:12Z","timestamp":1629668532000},"page":"2159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage"],"prefix":"10.3390","volume":"10","author":[{"given":"Elisa","family":"Balboa","sequence":"first","affiliation":[{"name":"Departamento de Gastroenterolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Gastroenterolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Esteban","family":"Oyarz\u00fan","sequence":"additional","affiliation":[{"name":"Departamento de Gastroenterolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1468-412X","authenticated-orcid":false,"given":"Pablo S.","family":"Contreras","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8018, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2939-7657","authenticated-orcid":false,"given":"Robert","family":"Hardt","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thea","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra R.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Department of Cellular and Molecular Biology, Biological Sciences Faculty, CARE UC, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8059-3202","authenticated-orcid":false,"given":"Boris","family":"Rebolledo-Jaramillo","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7710162, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9951-2174","authenticated-orcid":false,"given":"Andres D.","family":"Klein","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7710162, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6788-6641","authenticated-orcid":false,"given":"Dominic","family":"Winter","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8383-9829","authenticated-orcid":false,"given":"Silvana","family":"Zanlungo","sequence":"additional","affiliation":[{"name":"Departamento de Gastroenterolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/gim.2015.25","article-title":"High incidence of unrecognized visceral\/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets","volume":"18","author":"Wassif","year":"2015","journal-title":"Genet. 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