帕金森病（PD）黑质多巴胺（DA）能神经元死亡与SUR1/Kir6.2型KATP通道激活有关，PD病人残存的DA能神经元上SUR1 mRNA表达升高。我们前期实验发现，PD转基因小鼠在早期也出现黑质SUR1 mRNA水平上调，但机制不明。尽管在胰岛β细胞上发现FOXA1/2是SUR1的转录因子，FOXA1/2在DA能神经元发育及功能维持中非常重要，它是否也是DA能神经元SUR1的转录因子？为阐明SUR1 mRNA上调机制及在DA能神经元损伤中的作用，首先在DA能细胞上，观察FOXA1/2与SUR1启动子的结合及其对SUR1的表达调控，同时寻找其它转录因子。然后利用PD转基因及SUR1-/-小鼠，观察疾病进展中，FOXA1/2和SUR1的变化与DA能神经元功能变化之间的关系。本研究有望发现DA能神经元上SUR1特异性的转录因子，并阐明SUR1/Kir6.2型KATP通道致其损伤的机制。

In Parkinson’s disease (PD), the selective activation of SUR1/Kir6.2 subtype of ATP-sensitive potassium (KATP) channels in substantia nigra (SN) is involved in the degeneration of dopaminergic (DA) neurons. It is found that the mRNA levels of SUR1 subunit of KATP channels in the remaining DA neurons were transcriptionally increased in SN region of PD brains, but the mechanism is not known. In previous work, we found that the upregulation of SUR1 in SN was set on in the early stage of PD. Although FOXA1/2 functions as a transcriptional regulatory factor for SUR1 in pancreatic β cells, the effects of FOXA1/2 on SUR1 in DA neurons were currently not clarified. Because FOXA1/2 plays essential roles in the DA neurons’ development and functions, in this study, we first detect whether FOXA1/2 could regulate the expression of SUR1 subunit in DA cells, and other transcriptional factors will be screened. Furthermore, the causal association between changes in FOXA1/2 as well as SUR1 subunit expressions and the degeneration of DA neurons was studied. This study is expected to find out the specific transcription factor for SUR1, and illustrate the mechanism underlying SUR1/Kir6.2 type of KATP channels induced the selective degeneration of DA neurons in PD.