Science · 2007 · 1.1K citations · 22 references
Life SciencesMolecular BiologyNeuroscienceMolecular NeurobiologyMolecular NeuroscienceNeurodegenerationMolecular Basis Of NeurodegenerationNeurodegeneration MechanismsNeurodegenerative DiseasesNeurodegenerative DisordersParkinson DiseaseRna InterferenceAlpha-synuclein AggregationAlpha-synuclein MisfoldingDopaminergic Neuron DeathDrosophila Disease ModelsDrosophila ModelsParkinson Disease EpigeneticsSirtuin RegulationSirtuin Signaling
The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.
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α-Synuclein Locus Triplication Causes Parkinson's Disease
Andrew Singleton, Matthew J. Farrer, Janel Johnson et al. · Science · 2003 · 4.4K citations
A Drosophila model of Parkinson's disease
Mel Β. Feany, Welcome Bender · Nature · 2000 · 2.1K citations
The Human Sir2 Ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase
Brian J. North, Brett Marshall, Margie T. Borra et al. · Molecular Cell · 2003 · 1.5K citations · Full text