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Vitamin E dietary supplementation improves neurological symptoms and decreases c-Abl/p73 activation in niemann-pick C mice

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dc.contributor.author Marín, Tamara
dc.contributor.author Contreras, Pablo
dc.contributor.author Castro, Juan Francisco
dc.contributor.author Chamorro, David
dc.contributor.author Balboa, Elisa
dc.contributor.author Bosch Morató, Mònica, 1986-
dc.contributor.author Muñoz López, Francisco José, 1964-
dc.contributor.author Álvarez, Alejandra R.
dc.contributor.author Zanlungo, Silvana
dc.date.accessioned 2015-06-18T07:03:25Z
dc.date.available 2015-06-18T07:03:25Z
dc.date.issued 2014
dc.identifier.citation Marín T, Contreras P, Castro JF, Chamorro D, Balboa E, Bosch-Morató M et al. Vitamin E dietary supplementation improves neurological symptoms and decreases c-Abl/p73 activation in niemann-pick C mice. Nutrients. 2014; 6(8): 3000-3017. DOI 10.3390/nu6083000
dc.identifier.issn 2072-6643
dc.identifier.uri http://hdl.handle.net/10230/23852
dc.description.abstract 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 (α-TOH) supplemented diet and neurological symptoms, survival, Purkinje cell loss, α-TOH and nitrotyrosine levels, astrogliosis, and the c-Abl/p73 pathway functions were evaluated. In addition, the effect of α-TOH on the c-Abl/p73 pathway was evaluated in an in vitro NPC neuron model. The α-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 α-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 α-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.
dc.description.sponsorship This study was supported by grants from the Fondo Nacional de Desarrollo Científico y/nTecnológico (FONDECYT) (grant numbers 1120512 to A.R.A, and 1110310 to S.Z); Fondo de/nFomento al Desarrollo Científico y Tecnológico FONDEF D10I1077 (to A.R.A and S.Z.);/nFondo Nacional de Desarrollo de Areas Prioritarias, FONDAP, Project no. 15090007, Center for/nGenome Regulation (CGR) to S.Z.; Generalitat de Catalunya (SGR2009-1369) and La Marató de TV3/n(No. 100310)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Nutrients. 2014; 6(8): 3000-3017
dc.rights This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri https://creativecommons.org/licenses/by/3.0/
dc.subject.other Proteïna tirosina-quinasa -- Receptors
dc.subject.other Proteïnes de la sang
dc.title Vitamin E dietary supplementation improves neurological symptoms and decreases c-Abl/p73 activation in niemann-pick C mice
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/nu6083000
dc.subject.keyword Vitamin E
dc.subject.keyword Niemann-Pick C
dc.subject.keyword Cholesterol
dc.subject.keyword Lysosomes
dc.subject.keyword Apoptosis
dc.subject.keyword c-Abl
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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