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Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington’s Disease Models

Naia, Luana ; Rosenstock, Tatiana R. ; Oliveira, Ana M. ; Oliveira-Sousa, Sofia I. ; Caldeira, Gladys L. ; Carmo, Catarina ; Laço, Mário N. ; Hayden, Michael R. ; Oliveira, Catarina R. ; Rego, A. Cristina

Molecular neurobiology, 2017-09, Vol.54 (7), p.5385-5399 [Periódico revisado por pares]

New York: Springer US

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Título:
Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington’s Disease Models
Autor: Naia, Luana ; Rosenstock, Tatiana R. ; Oliveira, Ana M. ; Oliveira-Sousa, Sofia I. ; Caldeira, Gladys L. ; Carmo, Catarina ; Laço, Mário N. ; Hayden, Michael R. ; Oliveira, Catarina R. ; Rego, A. Cristina
Assuntos: Acetylation ; Activation ; Adenine ; Animal models ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Cell culture ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Deregulation ; Disease Models, Animal ; DNA, Mitochondrial - metabolism ; Electron transport ; Electron transport chain ; Embryos ; Humans ; Huntington Disease - genetics ; Huntington's disease ; Huntingtons disease ; Longevity ; Lymphoblasts ; Lysine ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Metabolism ; Mice ; Mice, Transgenic ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondrial DNA ; Motor skill learning ; Motor task performance ; NAD ; NADPH ; Neostriatum ; Neurobiology ; Neurology ; Neurons ; Neurons - drug effects ; Neurons - metabolism ; Neurosciences ; Niacinamide - pharmacology ; Nicotinamide ; Nicotinamide adenine dinucleotide ; Respiration ; Resveratrol ; Rodents ; Stilbenes - pharmacology ; Transcription ; Transgenic mice
É parte de: Molecular neurobiology, 2017-09, Vol.54 (7), p.5385-5399
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD + )-dependent lysine deacetylase that regulates longevity and enhances mitochondrial metabolism. Both activation and inhibition of SIRT1 were previously shown to ameliorate neuropathological mechanisms in Huntington’s disease (HD), a neurodegenerative disease that selectively affects the striatum and cortex and is commonly linked to mitochondrial dysfunction. Thus, in this study, we tested the influence of resveratrol (RESV, a SIRT1 activator) versus nicotinamide (NAM, a SIRT1 inhibitor) in counteracting mitochondrial dysfunction in HD models, namely striatal and cortical neurons isolated from YAC128 transgenic mice embryos, HD human lymphoblasts, and an in vivo HD model. HD cell models displayed a deregulation in mitochondrial membrane potential and respiration, implicating a decline in mitochondrial function. Further studies revealed decreased PGC-1α and TFAM protein levels, linked to mitochondrial DNA loss in HD lymphoblasts. Remarkably, RESV completely restored these parameters, while NAM increased NAD + levels, providing a positive add on mitochondrial function in in vitro HD models. In general, RESV decreased while NAM increased H3 acetylation at lysine 9. In agreement with in vitro data, continuous RESV treatment for 28 days significantly improved motor coordination and learning and enhanced expression of mitochondrial-encoded electron transport chain genes in YAC128 mice. In contrast, high concentrations of NAM blocked mitochondrial-related transcription, worsening motor phenotype. Overall, data indicate that activation of deacetylase activity by RESV improved gene transcription associated to mitochondrial function in HD, which may partially control HD-related motor disturbances.
Editor: New York: Springer US
Idioma: Inglês

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Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington’s Disease Models

Naia, Luana ; Rosenstock, Tatiana R. ; Oliveira, Ana M. ; Oliveira-Sousa, Sofia I. ; Caldeira, Gladys L. ; Carmo, Catarina ; Laço, Mário N. ; Hayden, Michael R. ; Oliveira, Catarina R. ; Rego, A. Cristina

New York: Springer US

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