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 |