摘要
Oxidative stress is now recognized as accountable for redox regulation involving reactive oxygen species (ROS) and reactive nitrogen species (RNS). Its role is pivotal for the modulation of critical cellular functions, notably for neurons astrocytes and microglia, such as apoptosis program activation, and ion transport, calcium mobilization, involved in excitotoxicity. Excitotoxicity and apoptosis are the two main causes of neuronal death. The role of mitochondria in apoptosis is crucial. Multiple apoptotic pathways emanate from the mitochondria. The respiratory chain of mitochondria that by oxidative phosphorylation, is the fount of cellular energy, i.e. ATP synthesis, is responsible for most of ROS and notably the first produced, superoxide anion (O2̇−). Mitochondrial dysfunction, i.e. cell energy impairment, apoptosis and overproduction of ROS, is a final common pathogenic mechanism in aging and in neurodegenerative disease such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Nitric oxide (NȮ), an RNS, which can be produced by three isoforms of NO-synthase in brain, plays a prominent role. The research on the genetics of inherited forms notably ALS, AD, PD, has improved our understanding of the pathobiology of the sporadic forms of neurodegenerative diseases or of aging of the brain. ROS and RNS, i.e. oxidative stress, are not the origin of neuronal death. The cascade of events that leads to neurons, death is complex. In addition to mitochondrial dysfunction (apoptosis), excitotoxicity, oxidative stress (inflammation), the mechanisms from gene to disease involve also protein misfolding leading to aggregates and proteasome dysfunction on ubiquinited material.
摘要译文
现在认为氧化应激对涉及活性氧（ROS）和活性氮物质（RNS）的氧化还原调节负责。其作用对于调节关键细胞功能至关重要，特别是对于神经元星形胶质细胞和小胶质细胞，例如凋亡程序激活，以及涉及兴奋性毒性的离子转运，钙动员。兴奋性毒性和细胞凋亡是神经元死亡的两个主要原因。线粒体在细胞凋亡中的作用至关重要。多个凋亡途径从线粒体发出。线粒体的呼吸链通过氧化磷酸化，是细胞能量的源，即ATP合成，是大多数ROS的原因，特别是第一个产生的超氧阴离子（O2 - ）。线粒体功能障碍，即细胞能量损伤，细胞凋亡和ROS的过量产生，是衰老和神经退行性疾病如阿尔茨海默病（AD），帕金森氏病（PD）和肌萎缩侧索硬化症（ALS）中的最终常见致病机制。一氧化氮（NO ̇）是一种RNS，可以通过脑中NO合酶的三种同种型产生，起着重要作用。遗传形式遗传学的研究，特别是ALS，AD，PD，已经提高了我们对散发形式的神经退行性疾病或大脑衰老的病理生物学的理解。 ROS和RNS，即氧化应激，不是神经元死亡的起源。导致神经元死亡的级联事件很复杂。除了线粒体功能障碍（细胞凋亡），兴奋性毒性，氧化应激（炎症），从基因到疾病的机制还涉及蛋白质错误折叠，导致泛素化材料上的聚集体和蛋白酶体功能障碍。
J.Emerit[a];M.Edeas[b][c];F.Bricaire[a];. Neurodegenerative diseases and oxidative stress[J]. Biomedicine & Pharmacotherapy, 2004,58(1): 39-46