线粒体解耦联蛋白2（Uncoupling protein 2, UCP2）是位于线粒体内膜上的质子转运蛋白，可使氧化磷酸化解耦联，减少ROS的产生并发挥抗氧化损伤作用。申请者在前期研究中发现UCP2缺失与帕金森病（Parkinson's disease, PD）的发生相关，新近又相继发现小鼠脑内星形胶质细胞和神经干细胞表达UCP2。本项目拟在前期研究基础上，应用已制备的UCP2敲除鼠建立MPTP/p PD模型，在整体、细胞和分子水平研究、阐明UCP2对中脑星形胶质细胞的能量代谢、氧化应激和胶质传递等功能的影响及对神经干细胞增殖、存活、迁移、分化的调节作用，揭示UCP2对胶质细胞功能和神经再生的调节与PD发生的相关性。研究成果不仅有助于深化对PD病理机制的认识，也为研发理想的多潜能神经保护剂提供新的靶标。

Mitochondrial uncoupling protein 2 (UCP2), which expressed in the inner membrane of mitochondria, is recognized to uncouple oxidative phosphorylation, inhibit reactive oxygen species (ROS) production and against oxidative damage. Our group had found UCP2 knockout exacerbated dopaminergic (DA) neuron degeneration in a MPTP/p mouse model, indicating that UCP2 may be involved in the pathogenesis of Parkinson's disease (PD). Currently, we found that UCP2 is also expressed in astrocytes and neural stem cells (NSCs). In the present study, we intend to investigate the regulatory effects of UCP2 on astrocyte-mediated oxidative stress, metabolic inflammation and gliotransmission with UCP2+/+ and UCP2-/- mice in vivo and in vitro. The modulation of UCP2 on NSC proliferation, survival, migration and differentiation will also be investigated in the project. We propose that UCP2 involves the pathogenesis of PD via regulating astrocytic function and neuroregeneration. These findings will give us an insight into the potential of UCP2 in the neuroprotection of PD.