Details

Autor(en) / Beteiligte

• 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
• Wang, Jian

Titel

Effect of Trehalose on PC12 Cells Overexpressing Wild-Type or A53T Mutant α-synuclein

Ist Teil von

• Neurochemical research, 2012-09, Vol.37 (9), p.2025-2032

Ort / Verlag

Boston: Springer US

Erscheinungsjahr

2012

Quelle

SpringerLink

Beschreibungen/Notizen

• 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.