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Nutrients 2014, 6(8), 3000-3017; https://doi.org/10.3390/nu6083000

Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice

1
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
2
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile
3
Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain
4
Center FONDAP for Genome Regulation, Santiago 8370415, Chile
*
Authors to whom correspondence should be addressed.
Received: 10 March 2014 / Revised: 16 July 2014 / Accepted: 18 July 2014 / Published: 30 July 2014
(This article belongs to the Special Issue Vitamin E Nutrition and Metabolism)
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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. View Full-Text
Keywords: vitamin E; Niemann-Pick C; cholesterol; lysosomes; apoptosis; c-Abl vitamin E; Niemann-Pick C; cholesterol; lysosomes; apoptosis; c-Abl
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Marín, T.; Contreras, P.; Castro, J.F.; Chamorro, D.; Balboa, E.; Bosch-Morató, M.; Muñoz, F.J.; Alvarez, A.R.; Zanlungo, S. Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice. Nutrients 2014, 6, 3000-3017.

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