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Effect of Trehalose on PC12 Cells Overexpressing Wild-Type or A53T Mutant α-synuclein.
MedLine Citation:
PMID:  22707286     Owner:  NLM     Status:  Publisher    
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.
Dan-Mei Lan; Feng-Tao Liu; Jian Zhao; Yan Chen; Jian-Jun Wu; Zheng-Tong Ding; Zhen-Yu Yue; Hui-Min Ren; Yu-Ping Jiang; Jian Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-17
Journal Detail:
Title:  Neurochemical research     Volume:  -     ISSN:  1573-6903     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, 200040, China.
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