Sirtuin 2 抑制剂 AK-7 在亨廷顿病小鼠模型中具有神经保护作用。
The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models.
机构信息
Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129-4404, USA.
出版信息
Cell Rep. 2012 Dec 27;2(6):1492-7. doi: 10.1016/j.celrep.2012.11.001. Epub 2012 Nov 29.
Abstract
Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. Our results provide preclinical validation of SIRT2 inhibition as a potential therapeutic target for HD and support the further development of SIRT2 inhibitors for testing in humans.
摘要
抑制组蛋白去乙酰化酶 SIRT2（SIRT2）可在帕金森病和亨廷顿病（HD）的细胞和无脊椎动物模型中发挥保护作用。在这里，我们报告了一种可穿透大脑的 SIRT2 抑制剂在两种 HD 遗传小鼠模型中的体内疗效。化合物治疗可改善运动功能、延长寿命、减少脑萎缩，并与标志性的 HD 病理学中聚集的突变型亨廷顿蛋白显著减少相关。我们的研究结果为 SIRT2 抑制作为 HD 的潜在治疗靶点提供了临床前验证，并支持进一步开发 SIRT2 抑制剂进行人体测试。
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