CeMM-Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, A-1090 Vienna, Austria.
Bioorg Med Chem. 2011 Jun 15;19(12):3616-24. doi: 10.1016/j.bmc.2011.01.018. Epub 2011 Jan 15.
Class III histone deacetylases (sirtuins) are becoming increasingly recognized as important epigenetic drug targets in cancer and metabolic disorders. As key regulators involved in numerous cellular signalling pathways, sirtuins are also emerging as potential targets in various neurodegenerative diseases such as Alzheimer, Parkinson's disease and others, thus suggesting modulation of sirtuin activity could provide an interesting and novel therapeutic option. In particular, much attention has been raised by neuroprotective effects attributed to SIRT1 activation due to genetically induced sirtuin overexpression or administration of resveratrol, a natural compound found in the skin of red grapes and also in wine. Similarly, also sirtuin inhibitors display benefits in various neuropathologic disease models. In light of the growing interest in sirtuin modulation and with regard to the lack of conclusive data on small molecule activators of sirtuins this review recapitulates the known facts about sirtuins and their relevance in neurodegenerative diseases.
III 类组蛋白去乙酰化酶（sirtuins）作为一种重要的表观遗传药物靶点，在癌症和代谢紊乱中受到越来越多的关注。作为涉及多种细胞信号通路的关键调节因子，sirtuins 也正在成为各种神经退行性疾病（如阿尔茨海默病、帕金森病等）的潜在靶点，这表明调节 sirtuin 活性可能提供一种有趣的新治疗选择。特别是由于基因诱导的 sirtuin 过表达或白藜芦醇（一种在红葡萄皮和葡萄酒中发现的天然化合物）的给药导致 SIRT1 激活的神经保护作用，引起了人们的极大关注。同样，sirtuin 抑制剂在各种神经病理疾病模型中也显示出益处。鉴于人们对 sirtuin 调节的兴趣日益浓厚，并且缺乏关于 sirtuins 的小分子激活剂的确凿数据，本综述总结了 sirtuins 的已知事实及其在神经退行性疾病中的相关性。
