Alpha-synuclein overexpression induced mitochondrial damage by the generation of endogenous neurotoxins in PC12 cells

作者：Zhang, Yanyan; Ma, Hong; Xie, Bingjie; Han, Chao; Wang, Chen; Qing, Hong; Deng, Yulin^*

来源：Neuroscience Letters, 2013, 547: 65-69.

DOI：10.1016/j.neulet.2013.05.012

• alpha-Synuclein
• Salsolinol
• NM-salsolinol
• Mitochondrial dysfunction

Alpha-synuclein is one of the important components of Lewy body which involved in neuropathology of Parkinson's disease (PD). The relationship between alpha-synuclein and cell death is still unclear. In the study, PC12 cell, stably over expressing alpha-synuclein model was used, and we investigated the level of intracellular oxidative stress, dopamine and endogenous neurotoxin. The results showed that the level of oxidative stress and intracytoplasmic dopamine (DA) was increased in cells over expressing alpha-synuclein compared with normal PC12 cells. Simultaneously, additional generation of endogenous neurotoxins 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolin (NM-salsolinol) was detected and this phenomenon was exacerbated after exposed to H2O2 for 24 h, but mitigated when treated with dopamine synthesis inhibitors. The presence of endogenous neurotoxins exacerbated alpha-synuclein induced mitochondrial damage. These results suggest that the endogenous neurotoxins may become a bridge between alpha-synuclein and cell death.

• 出版日期2013-6-28
• 单位北京理工大学