| 论文题目: | Activation of the macroautophagic system in scrapie-infected experimental animals and human genetic prion diseases |
|---|---|
| 作者: | Xu, Y; Tian, C; Wang, SB; Xie, WL; Guo, Y; Zhang, J; Shi, Q; Chen, C; Dong, XP |
| 联系作者: | Dong, XP |
| 刊物名称: | AUTOPHAGY |
| 期: | 11 |
| 卷: | 8 |
| 页: | 1604-1620 |
| 年份: | 2012 |
| 影响因子: | 7.453 |
| 论文下载: | 下载地址 |
| 摘要: | Macroautophagy is an important process for removing misfolded and aggregated protein in cells, the dysfunction of which has been directly linked to an increasing number of neurodegenerative disorders. However, the details of macroautophagy in prion diseases remain obscure. Here we demonstrated that in the terminal stages of scrapie strain 263K-infected hamsters and human genetic prion diseases, the microtubule-associated protein 1 light chain 3 (LC3) was converted from the cytosolic form to the autophagosome-bound membrane form. Macroautophagy substrate sequestosome 1 (SQSTM1) and polyubiquitinated proteins were downregulated in the brains of sick individuals, indicating enhanced macroautophagic protein degradation. The levels of mechanistic target of rapamycin (MTOR) and phosphorylated MTOR (p-MTOR) were significantly decreased, which implies that this enhancement of the macroautophagic response is likely through the MTOR pathway which is a negative regulator for the initiation of macroautophagy. Dynamic assays of the autophagic system in the brains of scrapie experimental hamsters after inoculation showed that alterations of the autophagic system appeared along with the deposits of PrPSc in the infected brains. Immunofluorescent assays revealed specific staining of autophagosomes in neurons that were not colocalized with deposits of PrPSc in the brains of scrapie infected hamsters, however, autophagosome did colocalize with PrPSc in a prion-infected cell line after treatment with bafilomycin A(1). These results suggest that activation of macroautophagy in brains is a disease-correlative phenomenon in prion diseases. |
京公网安备 11010502044263号