Transcriptome and proteome analysis in LUHMES cells overexpressing alpha-synculein

LUHMES cells share many characteritics with human dopamingeric neurons in the substantia nigra, the cells whose demise is responsible for the motor symptoms in Parkinson’s disease (PD). LUHMES cells can therefore be used bona fide as a model to study pathophysiological processes involved in PD. Previously, we showed that LUHMES cell degenerate after six days upon overexpression of wild type alpha-synuclein. In the present study we performed a transcriptome and proteome expression analysis in alpha-synuclein-overexpressing cells and GFP-expressing control cells in order to identify genes and proteins that are differentially regulated upon overexpression of alpha-synuclein. The analysis was performed four days after the initiation of alpha-synuclein or GFP overexpression, before the cells died in order to identify processes that preceded cell death.

LUHMES细胞与黑质（substantia nigra）内的人多巴胺能神经元（dopaminergic neurons）具有诸多共性，而这类神经元的丧失正是帕金森病（Parkinson’s disease, PD）运动症状的致病根源。因此，LUHMES细胞可作为研究帕金森病相关病理生理过程的真实可靠模型。此前本团队的研究证实，在过表达野生型α-突触核蛋白（alpha-synuclein）后，LUHMES细胞会在6天后发生退行性病变。本研究中，我们对过表达α-突触核蛋白的细胞与表达绿色荧光蛋白（GFP, green fluorescent protein）的对照细胞开展了转录组（transcriptome）与蛋白质组（proteome）表达分析，旨在筛选出α-突触核蛋白过表达后表达发生差异调控的基因与蛋白质。为了探明细胞死亡前的早期致病进程，我们在α-突触核蛋白或GFP过表达启动后的第4天完成了上述分析，此时细胞尚未发生死亡。