SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis
2007 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis
Kim, D.; Nguyen, M. D.; Dobbin, M. M.; Fischer, A. ; Sananbenesi, F. ; Rodgers, J. T. & Delalle, I. et al. (2007)
EMBO Journal, 26(13) pp. 3169-3179. DOI: https://doi.org/10.1038/sj.emboj.7601758
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Details
- Authors
- Kim, Dohoon; Nguyen, Minh Dang; Dobbin, Matthew M.; Fischer, Andre ; Sananbenesi, Farahnaz ; Rodgers, Joseph T.; Delalle, Ivana; Baur, Joseph A.; Sui, Guangchao; Armour, Sean M.; Puigserver, Pere; Sinclair, David A.; Tsai, Li-Huei
- Abstract
- A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.
- Issue Date
- 2007
- Journal
- EMBO Journal
- ISSN
- 0261-4189
- Language
- English