{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:22:35Z","timestamp":1782966155035,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2014,7,30]],"date-time":"2014-07-30T00:00:00Z","timestamp":1406678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Niemann-Pick C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of free cholesterol in lysosomes. We have previously reported that oxidative stress is the main upstream stimulus activating the proapoptotic c-Abl\/p73 pathway in NPC neurons. We have also observed accumulation of vitamin E in NPC lysosomes, which could lead to a potential decrease of its bioavailability. Our aim was to determine if dietary vitamin E supplementation could improve NPC disease in mice. NPC mice received an alpha-tocopherol (\u03b1-TOH) supplemented diet and neurological symptoms, survival, Purkinje cell loss, \u03b1-TOH and nitrotyrosine levels, astrogliosis, and the c-Abl\/p73 pathway functions were evaluated. In addition, the effect of \u03b1-TOH on the c-Abl\/p73 pathway was evaluated in an in vitro NPC neuron model. The \u03b1-TOH rich diet delayed loss of weight, improved coordination and locomotor function and increased the survival of NPC mice. We found increased Purkinje neurons and \u03b1-TOH levels and reduced astrogliosis, nitrotyrosine and phosphorylated p73 in cerebellum. A decrease of c-Abl\/p73 activation was also observed in the in vitro NPC neurons treated with \u03b1-TOH. In conclusion, our results show that vitamin E can delay neurodegeneration in NPC mice and suggest that its supplementation in the diet could be useful for the treatment of NPC patients.<\/jats:p>","DOI":"10.3390\/nu6083000","type":"journal-article","created":{"date-parts":[[2014,7,30]],"date-time":"2014-07-30T13:16:44Z","timestamp":1406726204000},"page":"3000-3017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl\/p73 Activation in Niemann-Pick C Mice"],"prefix":"10.3390","volume":"6","author":[{"given":"Tamara","family":"Mar\u00edn","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":"Pablo","family":"Contreras","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular y Molecular, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Castro","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":"David","family":"Chamorro","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular y Molecular, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Balboa","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":"M\u00f2nica","family":"Bosch-Morat\u00f3","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular y Molecular, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Zanlungo","sequence":"additional","affiliation":[{"name":"Departamento de Gastroenterolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"},{"name":"Center FONDAP for Genome Regulation, Santiago 8370415, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1474-4422(07)70194-1","article-title":"Miglustat for treatment of niemann-pick c disease: A randomised controlled study","volume":"6","author":"Patterson","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ymgme.2012.03.012","article-title":"Recommendations for the diagnosis and management of niemann-pick disease type c: An update","volume":"106","author":"Patterson","year":"2012","journal-title":"Mol. 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