{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:57:12Z","timestamp":1767855432394,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016991","name":"Universidad de Guadalajara","doi-asserted-by":"publisher","award":["PROSNI"],"award-info":[{"award-number":["PROSNI"]}],"id":[{"id":"10.13039\/100016991","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016991","name":"Universidad de Guadalajara","doi-asserted-by":"publisher","award":["PROINPEP-2025"],"award-info":[{"award-number":["PROINPEP-2025"]}],"id":[{"id":"10.13039\/100016991","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016991","name":"Universidad de Guadalajara","doi-asserted-by":"publisher","award":["CONACyT-M\u00e9xico Grant Ciencia de Frontera-2020-552265"],"award-info":[{"award-number":["CONACyT-M\u00e9xico Grant Ciencia de Frontera-2020-552265"]}],"id":[{"id":"10.13039\/100016991","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016991","name":"Universidad de Guadalajara","doi-asserted-by":"publisher","award":["1097536"],"award-info":[{"award-number":["1097536"]}],"id":[{"id":"10.13039\/100016991","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CONACyT M\u00e9xico","award":["PROSNI"],"award-info":[{"award-number":["PROSNI"]}]},{"name":"CONACyT M\u00e9xico","award":["PROINPEP-2025"],"award-info":[{"award-number":["PROINPEP-2025"]}]},{"name":"CONACyT M\u00e9xico","award":["CONACyT-M\u00e9xico Grant Ciencia de Frontera-2020-552265"],"award-info":[{"award-number":["CONACyT-M\u00e9xico Grant Ciencia de Frontera-2020-552265"]}]},{"name":"CONACyT M\u00e9xico","award":["1097536"],"award-info":[{"award-number":["1097536"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Niemann-Pick disease Type C (NPC) represents an autosomal recessive disorder with an incidence rate of 1 in 100,000 live births that belongs to the lysosomal storage diseases (LSDs). NPC is characterized by the abnormal accumulation of unesterified cholesterol, in addition to being an autosomal recessive inherited pathology, which belongs to LSDs. It occurs in 95% of cases due to mutations in the NPC1 gene, while 5% of cases are due to mutations in the NPC2 gene. In the cerebral cortex (CC), the disease shows lipid inclusions, increased cholesterol and multiple sphingolipids in neuronal membranes, and protein aggregates such as hyperphosphorylated tau, \u03b1-Synuclein, TDP-43, and \u03b2-amyloid peptide. Mitochondrial damage and oxidative stress are some alterations at the cellular level in NPC. Therefore, the aim of this work was to determine the gene expression profile in the CC of NPC1 mice in order to identify altered molecular pathways that may be related to the pathophysiology of the disease. Methods: In this study, we performed a microarray analysis of a 22,000-gene chip from the cerebral cortex of an NPC mutant mouse compared to a WT mouse. Subsequently, we performed a bioinformatic analysis in which we found groups of dysregulated genes, and their expression was corroborated by qPCR. Finally, we performed Western blotting to determine the expression of proteins probably dysregulated. Results: We found groups of dysregulated genes in the cerebral cortex of the NPC mouse involved in the ubiquitination, fatty acid metabolism, differentiation and development, and underexpression in genes with mitochondrial functions, which could be involved in intrinsic apoptosis reported in NPC, in addition, we found a generalized deregulation in the cortical circadian rhythm pathway, which could be related to the depressive behavior that has even been reported in NPC patients. Conclusions: Recognizing that there are changes in the expression of genes related to ubiquitination, mitochondrial functions, and cortical circadian rhythm in the NPC mutant mouse lays the basis for targeting treatments to new potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/genes16080865","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T10:28:09Z","timestamp":1753352889000},"page":"865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gene Expression Profile of the Cerebral Cortex of Niemann-Pick Disease Type C Mutant Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Iris Valeria","family":"Serv\u00edn-Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda Molecular, Instituto de Neurociencias Translacionales (INT), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Mexico"},{"name":"Doctorado en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-2514","authenticated-orcid":false,"given":"Daniel","family":"Ortu\u00f1o-Sahag\u00fan","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda Molecular, Instituto de Neurociencias Translacionales (INT), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8856-8722","authenticated-orcid":false,"given":"Mar\u00eda Paulina","family":"Reyes-Mata","sequence":"additional","affiliation":[{"name":"Departamento de Disciplinas Filos\u00f3fico, Metodol\u00f3gicas e Instrumentales, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-9130","authenticated-orcid":false,"given":"Christian","family":"Gri\u00f1\u00e1n-Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, Universitat de Barcelona, 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CiberNed), Network Center for Neurodegenerative Diseases, National Spanish Health Institute Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3095-4254","authenticated-orcid":false,"given":"Merc\u00e8","family":"Pall\u00e0s","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, Universitat de Barcelona, 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CiberNed), Network Center for Neurodegenerative Diseases, National Spanish Health Institute Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Gonz\u00e1lez-Castillo","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Campus Guadalajara, Zapopan 45201, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13023-018-0785-7","article-title":"International Niemann-Pick Disease Registry (INPDR) Consensus clinical management guidelines for Niemann-Pick disease type C","volume":"13","author":"Geberhiwot","year":"2018","journal-title":"Orphanet J. 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