Vitamin E dietary supplementation improves neurological symptoms and decreases c-Abl/p73 activation in Niemann-Pick C mice.
Nutrients
; 6(8): 3000-17, 2014 Jul 30.
Article
em En
| MEDLINE
| ID: mdl-25079853
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vitamina E
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Proteínas Nucleares
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Proteínas Proto-Oncogênicas c-abl
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Doenças Neurodegenerativas
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Suplementos Nutricionais
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Proteínas Supressoras de Tumor
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Proteínas de Ligação a DNA
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Doença de Niemann-Pick Tipo C
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nutrients
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Chile