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

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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.

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Abbreviations

α-Syn:

α-synuclein

PD:

Parkinson’s disease

WT:

Wild type

3-MA:

3-methyladenine

UPS:

Ubiquitin Proteasome System

ALS:

Autophagy Lysosome System

TEM:

Transmission electron microscope

DMSO:

Dimethyl sulfoxide

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium Bromide assay

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Acknowledgments

This study was supported by the grants (30600663, 81071018) from the Natural Science Foundation of China, Project (10PJ1401700) of Pujiang Talents at Shanghai, project (09411960900) from Science and Technology Commission of Shanghai Municipality, and project (2010-116) of Shanghai Municipal Health Bureau.

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  1. Dan-Mei Lan

    Present address: Department of Neurology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

Authors and Affiliations

  1. Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, 200040, China

    Dan-Mei Lan, Feng-Tao Liu, Jian Zhao, Yan Chen, Jian-Jun Wu, Zheng-Tong Ding, Hui-Min Ren, Yu-Ping Jiang & Jian Wang

  2. Department and Institute of Neurology, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, 200040, China

    Dan-Mei Lan, Feng-Tao Liu, Jian Zhao, Yan Chen, Jian-Jun Wu, Zheng-Tong Ding, Hui-Min Ren, Yu-Ping Jiang & Jian Wang

  3. Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Zhen-Yu Yue

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  1. Dan-Mei Lan
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Correspondence to Jian Wang.

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Dan-Mei Lan and Feng-Tao Liu have equal contribution to this work.

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Lan, DM., Liu, FT., Zhao, J. et al. Effect of Trehalose on PC12 Cells Overexpressing Wild-Type or A53T Mutant α-synuclein. Neurochem Res 37, 2025–2032 (2012). https://doi.org/10.1007/s11064-012-0823-0

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  • DOI: https://doi.org/10.1007/s11064-012-0823-0

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