SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice.
Huntington's disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modu...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0145425 |
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| author | Raffaella Tulino Agnesska C Benjamin Nelly Jolinon Donna L Smith Eduardo N Chini Alisia Carnemolla Gillian P Bates |
| author_facet | Raffaella Tulino Agnesska C Benjamin Nelly Jolinon Donna L Smith Eduardo N Chini Alisia Carnemolla Gillian P Bates |
| author_sort | Raffaella Tulino |
| collection | DOAJ |
| description | Huntington's disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies. |
| format | Article |
| id | doaj-art-fa4ad6c77f364fdf81ee63cfbb192c31 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-fa4ad6c77f364fdf81ee63cfbb192c312025-08-20T02:34:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014542510.1371/journal.pone.0145425SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice.Raffaella TulinoAgnesska C BenjaminNelly JolinonDonna L SmithEduardo N ChiniAlisia CarnemollaGillian P BatesHuntington's disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies.https://doi.org/10.1371/journal.pone.0145425 |
| spellingShingle | Raffaella Tulino Agnesska C Benjamin Nelly Jolinon Donna L Smith Eduardo N Chini Alisia Carnemolla Gillian P Bates SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice. PLoS ONE |
| title | SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice. |
| title_full | SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice. |
| title_fullStr | SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice. |
| title_full_unstemmed | SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice. |
| title_short | SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington's Disease Mice. |
| title_sort | sirt1 activity is linked to its brain region specific phosphorylation and is impaired in huntington s disease mice |
| url | https://doi.org/10.1371/journal.pone.0145425 |
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