دورية أكاديمية
Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway
| العنوان: | Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway |
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| المؤلفون: | Da Li, Ji-Jun Shi, Cheng-Jie Mao, Sha Liu, Jian-Da Wang, Jing Chen, Fen Wang, Ya-Ping Yang, Wei-Dong Hu, Li-Fang Hu, Chun-Feng Liu |
| المصدر: | International Journal of Molecular Sciences, Vol 14, Iss 12, Pp 24242-24254 (2013) |
| بيانات النشر: | MDPI AG, 2013. |
| سنة النشر: | 2013 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | dynein, α-synuclein, Parkinson’s disease, autophagy, autolysosome, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Growing evidence suggests that dynein dysfunction may be implicated in the pathogenesis of neurodegeneration. It plays a central role in aggresome formation, the delivery of autophagosome to lysosome for fusion and degradation, which is a pro-survival mechanism essential for the bulk degradation of misfolded proteins and damaged organells. Previous studies reported that dynein dysfuntion was associated with aberrant aggregation of α-synuclein, which is a major component of inclusion bodies in Parkinson’s disease (PD). However, it remains unclear what roles dynein plays in α-synuclein degradation. Our study demonstrated a decrease of dynein expression in neurotoxin-induced PD models in vitro and in vivo, accompanied by an increase of α-synuclein protein level. Dynein down-regulation induced by siRNA resulted in a prolonged half-life of α-synuclein and its over-accumulation in A53T overexpressing PC12 cells. Dynein knockdown also prompted the increase of microtubule-associated protein 1 light chain 3 (LC3-II) and sequestosome 1 (SQSTM1, p62) expression, and the accumulation of autophagic vacuoles. Moreover, dynein suppression impaired the autophagosome fusion with lysosome. In summary, our findings indicate that dynein is critical for the clearance of aberrant α-synuclein via autophagosome-lysosome pathway. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 |
| Relation: | http://www.mdpi.com/1422-0067/14/12/24242; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms141224242 |
| URL الوصول: | https://doaj.org/article/ef6af90b02a742e6b56c42dc0a63ea36 |
| رقم الأكسشن: | edsdoj.f6af90b02a742e6b56c42dc0a63ea36 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms141224242 |