| Title |
Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington’s Disease Models
|
|---|---|
| Published in |
Molecular Neurobiology, September 2016
|
| DOI | 10.1007/s12035-016-0048-3 |
| Pubmed ID | |
| Authors |
Luana Naia, Tatiana R. Rosenstock, Ana M. Oliveira, Sofia I. Oliveira-Sousa, Gladys L. Caldeira, Catarina Carmo, Mário N. Laço, Michael R. Hayden, Catarina R. Oliveira, A. Cristina Rego |
| Abstract |
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. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 103 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | <1% |
| Unknown | 102 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 12% |
| Researcher | 10 | 10% |
| Student > Master | 10 | 10% |
| Student > Bachelor | 10 | 10% |
| Professor > Associate Professor | 8 | 8% |
| Other | 20 | 19% |
| Unknown | 33 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 21 | 20% |
| Agricultural and Biological Sciences | 13 | 13% |
| Biochemistry, Genetics and Molecular Biology | 9 | 9% |
| Medicine and Dentistry | 8 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 5% |
| Other | 10 | 10% |
| Unknown | 37 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 December 2016.
All research outputs
#13,242,345
of 22,886,568 outputs
Outputs from Molecular Neurobiology
#1,649
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Outputs of similar age
#175,757
of 337,011 outputs
Outputs of similar age from Molecular Neurobiology
#56
of 108 outputs
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