Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice
AbstractNiemann-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
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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.
Marín T, Contreras P, Castro JF, Chamorro D, Balboa E, Bosch-Morató M, Muñoz FJ, Alvarez AR, Zanlungo S. Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice. Nutrients. 2014; 6(8):3000-3017.Chicago/Turabian Style
Marín, Tamara; Contreras, Pablo; Castro, Juan F.; Chamorro, David; Balboa, Elisa; Bosch-Morató, Mònica; Muñoz, Francisco J.; Alvarez, Alejandra R.; Zanlungo, Silvana. 2014. "Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice." Nutrients 6, no. 8: 3000-3017.