Journal
NUTRIENTS
Volume 6, Issue 8, Pages 3000-3017Publisher
MDPI AG
DOI: 10.3390/nu6083000
Keywords
vitamin E; Niemann-Pick C; cholesterol; lysosomes; apoptosis; c-Abl
Categories
Funding
- Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1120512, 1110310]
- Fondo de Fomento al Desarrollo Cientifico y Tecnologico FONDEF [D10I1077]
- Fondo Nacional de Desarrollo de Areas Prioritarias, FONDAP, Center for Genome Regulation (CGR) [15090007]
- Generalitat de Catalunya [SGR2009-1369]
- La Marato de TV3 [100310]
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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 (alpha-TOH) supplemented diet and neurological symptoms, survival, Purkinje cell loss, alpha-TOH and nitrotyrosine levels, astrogliosis, and the c-Abl/p73 pathway functions were evaluated. In addition, the effect of alpha-TOH on the c-Abl/p73 pathway was evaluated in an in vitro NPC neuron model. The alpha-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 alpha-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 alpha-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.
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