Barnstable Colin J
Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA 17033 USA.
J Ocul Biol Dis Infor. 2009 Sep;2(3):145-148. doi: 10.1007/s12177-009-9036-4. Epub 2009 Sep 18.
Neuronal cell death can be determined by the overall level of reactive oxygen species (ROS) resulting from the combination of extrinsic sources and intrinsic production as a byproduct of oxidative phosphorylation. Key controllers of the intrinsic production of ROS are the mitochondrial uncoupling proteins (UCPs). By allowing a controlled leak of protons across the inner mitochondrial membrane activation of these proteins can decrease ROS and promote cell survival. In both primate models of Parkinson's disease and mouse models of seizures, increased activity of UCP2 significantly increased neuronal cells survival. In the retina UCP2 is expressed in many neurons and glial cells, but was not detected in rod photoreceptors. Retinal ganglion cell survival following excitotoxic damage was much greater in animals overexpressing UCP2. Traditional Chinese medicines, such as an extract of Cistanche tubulosa, may provide benefit by altering mitochondrial metabolism.
神经元细胞死亡可由外部来源与作为氧化磷酸化副产物的内源性产生相结合所产生的活性氧（ROS）的总体水平来确定。ROS内源性产生的关键调控因子是线粒体解偶联蛋白（UCPs）。通过允许质子受控地穿过线粒体内膜，这些蛋白的激活可以减少ROS并促进细胞存活。在帕金森病的灵长类动物模型和癫痫的小鼠模型中，UCP2活性增加均显著提高了神经元细胞的存活率。在视网膜中，UCP2在许多神经元和胶质细胞中表达，但在视杆光感受器中未检测到。在过表达UCP2的动物中，兴奋性毒性损伤后的视网膜神经节细胞存活率要高得多。传统中药，如肉苁蓉提取物，可能通过改变线粒体代谢而发挥作用。
