Neuroprotection of alpha-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K

作者：Choong Chi Jing; Say Yee How^*

来源：NeuroToxicology, 2011, 32(6): 857-863.

DOI：10.1016/j.neuro.2011.05.012

• alpha-Synuclein
• Parkinson's disease
• Rotenone
• Maneb
• Oxidative stress
• Reactive oxygen species

alpha-Synuclein (alpha-Syn) plays a crucial role in the pathophysiology of Parkinson's disease (PD). alpha-Syn has been extensively studied in many neuronal cell-based PD models but has yielded mixed results. The objective of this study was to re-evaluate the dual cytotoxic/protective roles of alpha-Syn in dopaminergic SH-SY5Y cells. Stable SH-SY5Y cells overexpressing wild type or familial alpha-Syn mutants (A30P, E46K and A53T) were subjected to acute and chronic rotenone and maneb treatment. Compared with untransfected SH-SY5Y cells, wild type alpha-Syn attenuated rotenone and maneb-induced cell death along with an attenuation of toxin-induced mitochondrial membrane potential changes and Reactive Oxygen Species level, whereas the mutant alpha-Syn constructs exacerbated environmental toxins-induced cytotoxicity. After chronic treatment, wild type alpha-Syn but not the mutant variants was found to rescue cells from subsequent acute hydrogen peroxide insult. These results suggest that the fundamental property of wild type alpha-Syn may be protective, and such property may be lost by its familial PD mutations.

• 出版日期2011-12