151. Effect of Trehalose on PC12 Cells Overexpressing Wild-Type or A53T Mutant α-synuclein.
- Author
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Lan, Dan-Mei, Liu, Feng-Tao, Zhao, Jian, Chen, Yan, Wu, Jian-Jun, Ding, Zheng-Tong, Yue, Zhen-Yu, Ren, Hui-Min, Jiang, Yu-Ping, and Wang, Jian
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TREHALOSE , *GENE expression , *SYNUCLEINS , *PARKINSON'S disease , *AUTOPHAGY , *PROTEASOME inhibitors - Abstract
Accumulation of α-synuclein (α-Syn) is a common pathology for both familiar and sporadic Parkinson's disease (PD), enhancing its clearance might be a promising strategy for treating PD. To assess the potential of trehalose in this regard, we investigated its effect on the PC12 cells overexpressing wild type (WT) or A53T mutant α-Syn and the implicated pathway it might mediated. We observed that trehalose promoted the clearance of A53T α-Syn but not WT α-Syn in PC12 cells, and confirmed the increased LC3 and Lysotracker RED positive autolysosomes by using lysotracker and LC3 staining, the enhanced expression of LC3-II in Western blot, and more autophagosomes under Transmission Electron Microscope in a dose dependent manner after the trehalose treatment. The activation of autophagy can be alleviated by applying macroautophagy inhibitor 3-methyladenine (3-MA). In addition, degradation of A53T and WT α-Syn was blocked after Ubiquitin Proteasome System (UPS) inhibitor (MG132) was applied in those PC12 cells overexpressing A53T or WT α-Syn, suggesting that A53T α-Syn could be degraded by both UPS and macroautophagy. But the effect of trehalose on A53T α-Syn is mainly mediated through the macroautophagy pathway, which is not a dominant way for WT α-Syn clearance. Further in vivo research will be needed to verify the effectiveness of trehalose in treating PD. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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