Sirtuin 2 inhibitors rescue α-synuclein-mediated toxicity in models of Parkinson's disease
Sirtuin 2 inhibitors rescue α-synuclein-mediated toxicity in models of Parkinson's disease
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DOI：
10.1126/science.1143780
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发表时间：
2007-07-27
期刊：
影响因子：
56.9
通讯作者：
Kazantsev, Aleksey G.
中科院分区：
文献类型：
--
作者：
Outeiro, Tiago Fleming;Kontopoulos, Eirene;Kazantsev, Aleksey G.
sirtuins是组蛋白去乙酰化酶家族的成员，参与多种细胞功能并在衰老中发挥作用。我们确定了sirtuin 2 （SIRT2）的有效抑制剂，并发现SIRT2的抑制可挽救帕金森病细胞模型中的α -突触核蛋白毒性并改变包涵体形态。通过小干扰RNA对SIRT2的遗传抑制同样挽救了α -突触核蛋白毒性。此外，抑制剂在体外和帕金森病的果蝇模型中都能防止多巴胺能细胞死亡。研究结果表明，神经退化和衰老之间存在联系。
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.