过度兴奋与神经元功能障碍有关,细胞死亡,因此神经变性。氧化还原失衡可导致兴奋过度,在各种神经系统疾病中观察到活性氧(ROS)水平增加。NOX4是已知产生ROS的NADPH氧化酶,并且在氧化应激期间可能具有调节功能。我们,因此,旨在确定NOX4对神经元放电的作用,过度兴奋,和过度兴奋引起的神经网络功能变化。使用体内兴奋过度模型的多维方法,蛋白质组学分析,和ROS的细胞功能分析,线粒体完整性,和钙水平,我们证明,NOX4通过调节ROS和钙稳态,从而防止过度兴奋和随后的神经元死亡而具有神经保护作用。这些结果暗示NOX4是一种潜在的氧化还原调节剂,有利于过度兴奋,因此可能在神经变性中起重要作用。
Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration.