{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:22:36Z","timestamp":1782966156680,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2016-77703"],"award-info":[{"award-number":["SAF2016-77703"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["PID2019-106285RB"],"award-info":[{"award-number":["PID2019-106285RB"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2017SGR106"],"award-info":[{"award-number":["2017SGR106"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013816","name":"Departament d'Empresa i Coneixement, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["Llavor 00007(2018)"],"award-info":[{"award-number":["Llavor 00007(2018)"]}],"id":[{"id":"10.13039\/501100013816","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann\u2013Pick type C (NPC) disease is a rare autosomal recessive inherited childhood neurodegenerative disease characterized by the accumulation of cholesterol and glycosphingolipids, involving the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 12-diols, exerts beneficial effects in modulating inflammation and autophagy, critical features of the NPC disease. This study aims to evaluate the effects of UB-EV-52, an sEH inhibitor (sEHi), in an NPC mouse model (Npc) by administering it for 4 weeks (5 mg\/kg\/day). Behavioral and cognitive tests (open-field test (OF)), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that the treatment produced an improvement in short- and long-term memory as well as in spatial memory. Furthermore, UB-EV-52 treatment increased body weight and lifespan by 25% and reduced gene expression of the inflammatory markers (i.e., Il-1\u03b2 and Mcp1) and enhanced oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. As for autophagic markers, surprisingly, we found significantly reduced levels of LC3B-II\/LC3B-I ratio and significantly reduced brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in treated Npc mice group compared to untreated ones in hippocampal tissue. Lipid profile analysis showed a significant reduction of lipid storage in the liver and some slight changes in homogenated brain tissue in the treated NPC mice compared to the untreated groups. Therefore, our results suggest that pharmacological inhibition of sEH ameliorates most of the characteristic features of NPC mice, demonstrating that sEH can be considered a potential therapeutic target for this disease.<\/jats:p>","DOI":"10.3390\/ijms22073409","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T06:59:42Z","timestamp":1616741982000},"page":"3409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of Soluble Epoxide Hydrolase Ameliorates Phenotype and Cognitive Abilities in a Murine Model of Niemann Pick Type C Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-9130","authenticated-orcid":false,"given":"Christian","family":"Gri\u00f1\u00e1n-Ferr\u00e9","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Section and Institute of Neuroscience, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-7700","authenticated-orcid":false,"given":"J\u00falia","family":"Companys-Alemany","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Section and Institute of Neuroscience, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Jarn\u00e9-Ferrer","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Section and Institute of Neuroscience, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Codony","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry (CSIC, Associated Unit), Faculty of Pharmacy and Food Sciences and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Gonz\u00e1lez-Castillo","sequence":"additional","affiliation":[{"name":"Tecnol\u00f3gico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Campus Guadalajara, Zapopan, 45201 Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Investigaci\u00f3n en Ciencias Biom\u00e9dicas (IICB), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Jalisco 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00efsa","family":"Vilageliu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institut de Biomedicina de la UB (IBUB)-Institut de Recerca Sant Joan de D\u00e9u (IRSJD), 08028 Barcelona, Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-2590","authenticated-orcid":false,"given":"Daniel","family":"Grinberg","sequence":"additional","affiliation":[{"name":"Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institut de Biomedicina de la UB (IBUB)-Institut de Recerca Sant Joan de D\u00e9u (IRSJD), 08028 Barcelona, Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-6026","authenticated-orcid":false,"given":"Santiago","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry (CSIC, Associated Unit), Faculty of Pharmacy and Food Sciences and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3095-4254","authenticated-orcid":false,"given":"Merc\u00e8","family":"Pall\u00e0s","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Section and Institute of Neuroscience, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1034\/j.1399-0004.2003.00147.x","article-title":"Niemann\u2013Pick disease type C","volume":"64","author":"Vanier","year":"2003","journal-title":"Clin. 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