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

Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile
Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain
Center FONDAP for Genome Regulation, Santiago 8370415, Chile
Authors to whom correspondence should be addressed.
Nutrients 2014, 6(8), 3000-3017;
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)
PDF [2300 KB, uploaded 30 July 2014]


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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