Degradation of TDP-43 and its pathogenic form by autophagy and the ubiquitin-proteasome system

作者：Wang Xiaoju; Fan Huadong; Ying Zheng; Li Bin; Wang Hongfeng; Wang Guanghui^*

来源：Neuroscience Letters, 2010, 469(1): 112-116.

DOI：10.1016/j.neulet.2009.11.055

• TDP-43
• Ubiquitin-proteasome
• Autophagy

TAR DNA-binding protein-43 (TDP-43) is a nuclear protein functioning in the regulation of transcription and mRNA splicing. TDP-43 is accumulated in ubiquitinated inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyrotrophic lateral sclerosis (ALS) diseased brains. However, the pathways involved in the clearance of TDP-43 and its pathogenic form (TDP-25), a truncated form of TDP-43, are still not elucidated. In this study, we demonstrated that the protein levels of TDP-43 and TDP-25 were increased in cells treated with a proteasome inhibitor, MG132, or an autophagy inhibitor, 3-MA, whereas, they were decreased in cells treated with an enhancer of autophagy, trehalose. Furthermore. more protein level changes of TDP-25 than TDP-43 were observed in cells treated with above inhibitors or enhancer. Thus, our data suggest that TDP-43 and TDP-25 are degraded by both proteasome and autophagy with TDP-25 being more regulated.

• 出版日期2010-1-18
• 单位中国科学技术大学