CAJ | 학술논문

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 ataxia 3/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 .
목적 탐토자탄서도경(autophagy)재척수소뇌형공제실조3형혹칭마사다-약슬부병(spinocerebellar ataxia 3/Machado-Joseph disease,SCA3/MJD)발병궤제중적작용.방법 장CAG고패수68차적ataxin-3진핵표체재체pcDNA3.1-Myc-His(B)-MJD68Q재HEK293세포중표체,채용특이성자탄서도경억제제급격활제처리세포후,검측세포중ataxin-3-68Q적표체수평.결과 억제자탄서도경수평,세포내ataxin-3-68Q표체명현증가,세포활성강저;반지역연.결론 자탄서도경삼여강해세포내다취곡안선알확전돌변형ataxin-3,감소포내취합물적형성,종이감경세포독성.인차,제고궤체자탄서도경수평유망작위치료SCA3/MJD적신방법 .
Objective To investigate the role of autophagy on the pathogenesis of spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD). Methods HEK293 cells expressing polyglutamineexpanded ataxin-3 were used as cell model for SCA3/MJD. The level of polyglutamine-expanded ataxin-3was 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 ataxin3, 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.