Effect of trehalose on PC12 cells overexpressing wild-type or A53T mutant α-synuclein.
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.
Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai 200040, China.
Dan-Mei
DM
Lan
Feng-Tao
FT
Liu
Jian
J
Zhao
Yan
Y
Chen
Jian-Jun
JJ
Wu
Zheng-Tong
ZT
Ding
Zhen-Yu
ZY
Yue
Hui-Min
HM
Ren
Yu-Ping
YP
Jiang
Jian
J
Wang
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000409:Alanine; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D008247:Lysosomes / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D016716:PC12 Cells; D010588:Phagosomes / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017354:Point Mutation; D061988:Proteasome Inhibitors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D013912:Threonine; D014161:Transduction, Genetic; D014199:Trehalose / Q000494:pharmacology*; D015854:Up-Regulation; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000235:genetics*
D000081082:Phosphoinositide-3 Kinase Inhibitors; D061988:Proteasome Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D051844:alpha-Synuclein; D013912:Threonine; C025946:3-methyladenine; D014199:Trehalose; C022616:thiazolyl blue; D000225:Adenine; D000409:Alanine