INSERM, Laboratory of Neuronal Cell Biology and Pathology, Center for Psychiatry and Neurosciences U894, Paris, France.
J Med Chem. 2010 Feb 11;53(3):1407-11. doi: 10.1021/jm9013345.
In oculopharyngeal muscular dystrophy (OPMD), a disease caused by polyalanine expansion in the nuclear protein PABPN1, the genetic inhibition of sirtuins and treatment with sirtuin inhibitors protect from mutant PABPN1 toxicity in transgenic nematodes. Here, we tested the SIRT1/2 inhibitors 1-12, bearing different degrees of inhibition, for protection against mutant PABPN1 toxicity in Caenorhabditis elegans. Compounds 2, 4, and 11 were the most efficient, revealing a potential therapeutic application for muscle cell protection in OPMD.
在眼咽型肌营养不良症（OPMD）中，一种由核蛋白 PABPN1 中的多聚丙氨酸扩展引起的疾病，抑制 sirtuins 的遗传和使用 sirtuin 抑制剂可防止转染线虫中突变型 PABPN1 的毒性。在这里，我们测试了具有不同抑制程度的 SIRT1/2 抑制剂 1-12，以防止 Caenorhabditis elegans 中的突变型 PABPN1 毒性。化合物 2、4 和 11 最为有效，这为 OPMD 的肌肉细胞保护提供了潜在的治疗应用。
