Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Perak Campus, 31900 Kampar, Perak, Malaysia.
Neurotoxicology. 2011 Dec;32(6):857-63. doi: 10.1016/j.neuro.2011.05.012. Epub 2011 May 30.
α-Synuclein (α-Syn) plays a crucial role in the pathophysiology of Parkinson's disease (PD). α-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 α-Syn in dopaminergic SH-SY5Y cells. Stable SH-SY5Y cells overexpressing wild type or familial α-Syn mutants (A30P, E46K and A53T) were subjected to acute and chronic rotenone and maneb treatment. Compared with untransfected SH-SY5Y cells, wild type α-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 α-Syn constructs exacerbated environmental toxins-induced cytotoxicity. After chronic treatment, wild type α-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 α-Syn may be protective, and such property may be lost by its familial PD mutations.
α-突触核蛋白（α-Syn）在帕金森病（PD）的病理生理学中起着至关重要的作用。α-Syn 在许多基于神经元细胞的 PD 模型中得到了广泛研究，但结果喜忧参半。本研究的目的是重新评估α-Syn 在多巴胺能 SH-SY5Y 细胞中的双重细胞毒性/保护作用。稳定过表达野生型或家族性α-Syn 突变体（A30P、E46K 和 A53T）的 SH-SY5Y 细胞分别接受急性和慢性鱼藤酮和代森锰处理。与未转染的 SH-SY5Y 细胞相比，野生型α-Syn 减轻了鱼藤酮和代森锰诱导的细胞死亡，同时减轻了毒素诱导的线粒体膜电位变化和活性氧水平的升高，而突变型α-Syn 构建体则加剧了环境毒素诱导的细胞毒性。慢性处理后，发现野生型α-Syn 而非突变型变体能够挽救细胞免受随后的急性过氧化氢损伤。这些结果表明，野生型α-Syn 的基本特性可能是保护性的，而这种特性可能会因其家族性 PD 突变而丧失。
