中文摘要：

目的 探索肌萎缩侧索硬化症（ALS）相关TDP-43的降解机制.方法 用瞬时转染的方法在运动神经元样细胞系NSC-34中过表达野生型（role of wild-type,WT） WT TDP-43,与家族型ALS相关的Q331K TDP-43、M337V TDP-43突变蛋白、TDP-43的两种C末端片段TDP-25和TDP-35,再给予自噬、蛋白酶体通路的特异性诱导剂和阻断剂,通过蛋白印迹方法检测5种TDP-43以及自噬标记物LC3-Ⅱ的表达水平.结果 在自噬诱导剂作用下,各组LC3-Ⅱ的表达升高,同时两种突变TDP-43及其C末端片段的表达明显减少,在自噬通路和蛋白酶体阻断剂作用下突变TDP-43及其C末端片段表达水平明显增多,而WT TDP-43的蛋白表达水平仅在蛋白酶体阻断剂作用时增多.结论 WT TDP-43主要经由蛋白酶体途径降解,Q331K TDP-43、M337V TDP-43及其C末端片段经由蛋白酶体途径和自噬两种途径降解.

英文摘要：

Objective To explore the degradation mechanism of TDP-43 related to ALS pathogenesis. Methods NSC-34 cells transient-transfected with WT TDP-43, Q331K TDP-43, M337V TDP-43, TDP-25 and TDP-35 were treated with autophagy or proteasome inducer and blocker, the level of various disease-related TDP-43 and LC3-II was measured by Western blot. Results With the effect of autophagy inducer, the expression level of LC3-II increases, and the two mutant TDP-43 （Q331K TDP-43 and M337V TDP-43） and their C-terminal fragments＇ expression level decreased significantly. And the expression level of the mutant TDP-43 and their C-terminal fragments evidently increased with the effect of the autophagy pathway and the proteasome blocker, but the expression level of the WT TDP-43 protein rises only when the proteasome blocker works there. Conclusion WT TDP-43 is mainly degraded through proteasome pathway, but the ALS-related TDP-43 and their C-terminal fragments are degraded through both proteasome pathway and autophagy.