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Int. J. Mol. Sci. 2013, 14(12), 24242-24254; doi:10.3390/ijms141224242
Article

Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway

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Received: 11 September 2013; in revised form: 26 November 2013 / Accepted: 3 December 2013 / Published: 13 December 2013
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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Abstract: 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.
Keywords: dynein; α-synuclein; Parkinson’s disease; autophagy; autolysosome dynein; α-synuclein; Parkinson’s disease; autophagy; autolysosome
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Li, D.; Shi, J.-J.; Mao, C.-J.; Liu, S.; Wang, J.-D.; Chen, J.; Wang, F.; Yang, Y.-P.; Hu, W.-D.; Hu, L.-F.; Liu, C.-F. Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway. Int. J. Mol. Sci. 2013, 14, 24242-24254.

AMA Style

Li D, Shi J-J, Mao C-J, Liu S, Wang J-D, Chen J, Wang F, Yang Y-P, Hu W-D, Hu L-F, Liu C-F. Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway. International Journal of Molecular Sciences. 2013; 14(12):24242-24254.

Chicago/Turabian Style

Li, Da; Shi, Ji-Jun; Mao, Cheng-Jie; Liu, Sha; Wang, Jian-Da; Chen, Jing; Wang, Fen; Yang, Ya-Ping; Hu, Wei-Dong; Hu, Li-Fang; Liu, Chun-Feng. 2013. "Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway." Int. J. Mol. Sci. 14, no. 12: 24242-24254.


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