Effect of trehalose on PC12 cells overexpressing wild-type or A53T mutant α-synuclein

Neurochem Res. 2012 Sep;37(9):2025-32. doi: 10.1007/s11064-012-0823-0. Epub 2012 Jun 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Alanine
  • Animals
  • Autophagy / drug effects
  • Blotting, Western
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fluorescent Antibody Technique
  • Lysosomes / metabolism
  • Microscopy, Electron, Transmission
  • PC12 Cells
  • Phagosomes / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Point Mutation*
  • Proteasome Inhibitors / pharmacology
  • Rats
  • Signal Transduction / drug effects
  • Tetrazolium Salts
  • Thiazoles
  • Threonine
  • Transduction, Genetic
  • Trehalose / pharmacology*
  • Up-Regulation
  • alpha-Synuclein / biosynthesis*
  • alpha-Synuclein / genetics*


  • Phosphoinositide-3 Kinase Inhibitors
  • Proteasome Inhibitors
  • Tetrazolium Salts
  • Thiazoles
  • alpha-Synuclein
  • Threonine
  • 3-methyladenine
  • Trehalose
  • thiazolyl blue
  • Adenine
  • Alanine