中文摘要：

目的探讨自吞噬途径（autophagy）在脊髓小脑型共济失调3型或称马查多-约瑟夫病（spinocerebellar ataxia3／Machado—Joseph disease，SCA3／MJD）发病机制中的作用。方法将CAG拷贝数68次的ataxin-3真核表达载体pcDNA3．1-Myc-His（B）-MJD68Q在HEK293细胞中表达，采用特异性自吞噬途径抑制剂及激活剂处理细胞后，检测细胞中ataxin-3-68Q的表达水平。结果抑制自吞噬途径水平，细胞内ataxin-3—68Q表达明显增加，细胞活性降低；反之亦然。结论自吞噬途径参与降解细胞内多聚谷氨酰胺扩展突变型ataxin-3，减少胞内聚合物的形成，从而减轻细胞毒性。因此，提高机体自吞噬途径水平有望作为治疗SCA3／MJD的新方法。

英文摘要：

Objective To investigate the role of autophagy on the pathogenesis of spinocerebellar ataxia 3/Machado-Joseph disease （SCA3/MJD）. Methods HEK293 cells expressing polyglutamine- expanded ataxin-3 were used as cell model for SCA3/MJD. The level of polyglutamine-expanded ataxin-3 was detected after cells were treated with different inhibitors or inducer of autophagy. Results Inhibition of autophagy increased aggregate formation and cell death in HEK293 cells expressing mutated ataxin-3, and vice versa. Conclusion The data suggested that autophagy is involved in the degradation of mutant ataxin- 3, resulting in a decrease in the proportions of aggregate-containing cells and cell death in HEK293 cells expressing polyglutamine-expanded ataxin 3. It is possible that autophagy may be applied as a potential therapeutic approach for SCA3/MJD.