Elucidation of pathogenesis and therapy development of sporadic ALS by disease model

在本研究中，我们建立了一个秀丽隐杆线虫模型，其中DNC-1 （dynactin 1的同系物）的表达在运动神经元中被特异性地敲低。该模型表现出严重的运动缺陷，并伴有轴突和神经元变性。我们还观察到退化神经元的运动受损和自噬体数量增加。此外，自噬激活剂雷帕霉素和促进轴突运输的曲古霉素联合使用可显著改善该模型的运动表型和轴突变性。

In the present study, we generated a Caenorhabditis elegans model in which the expression of DNC-1, the homolog of dynactin 1, is specifically knocked down in motor neurons. This model exhibited severe motor defects together with axonal and neuronal degeneration. We also observed impaired movement and increased number of autophagosomes in the degenerated neurons. Furthermore, the combination of rapamycin, an activator of autophagy, and trichostatin which facilitates axonal transport dramatically ameliorated the motor phenotype and axonal degeneration of this model.