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- Title
Sirt1âs Complex Roles in Neuroprotection.
- Authors
Bor Tang
- Abstract
Abstract  The nicotinamide adenine dinucleotide (NAD)-activated protein deacetylase Sir2p/Sirt1 has been strongly implicated in the modulation of replicative lifespan and promotion of longevity. Part of Sirt1âs capacity for lifespan extension in complex organisms may be attributed to its protective activity against neuronal degeneration. Manipulation of Sirt1âs activity or levels by pharmacological and genetic means in several models of neurodegenerative diseases demonstrated its neuroprotective credentials. However, recent data have indicated that under certain contexts, Sirt1 inhibition, rather than activation, is neuroprotective. These inconsistencies highlight the complex nature of Sirt1-mediated effects. The enzyme has both histone and nonhistone targets, and could potentially act in both nuclear and cytoplasmic compartments. These activities intertwine in a manner depending on the context of a system under investigation. One needs to be cautious in extrapolating results derived from short-term observations to a longer-term context, and in assessing efficacies of Sirt1-based therapeutic approaches in treating neurodegenerative diseases.
- Subjects
NEUROPROTECTIVE agents; NEUROLOGY; NAD (Coenzyme); NEURODEGENERATION; NONHISTONE chromosomal proteins; LONGEVITY
- Publication
Cellular & Molecular Neurobiology, 2009, Vol 29, Issue 8, p1093
- ISSN
0272-4340
- Publication type
Article
- DOI
10.1007/s10571-009-9414-2