Zekry Dina, Epperson Terry Kay, Krause Karl-Heinz
Department of Geriatrics, Geneva University Hospitals, Switzerland.
IUBMB Life. 2003 Jun;55(6):307-13. doi: 10.1080/1521654031000153049.
Because of population ageing, dementias are likely to become a major scourge of the 21st century. Causes of dementia include Alzheimer's disease, cerebrovascular disease, and lesser known entities such as frontotemporal dementia or dementia with Lewy bodies. Neuroinflammation is likely to play an important role in the pathogenesis of dementia by the killing of neurons through inflammatory mechanisms. Such a role of neuroinflammation is well documented for Alzheimer's disease, and it is likely to play a role in other types of dementia as well. Reactive oxygen species (ROS) play a key role in inflammatory tissue destruction. The phagocyte NADPH oxidase NOX2 is the best studied ROS-generating system. In the central nervous system, it is expressed in microglia and--to a lesser extent--in neurons. Indeed, there is emerging experimental evidence for a role of NOX2 in Alzheimer's and cerebrovascular disease. Recently, six novel ROS-generating NADPH oxidases with homology to NOX2 have been discovered. Several of them are also expressed in the central nervous system. In this article, we hypothesize a role of NOX-type NADPH oxidases in inflammatory neuronal loss. We review presently available evidence and suggest that NOX-type NADPH oxidases may become promising pharmacological targets for the treatment and prevention of dementia.
由于人口老龄化，痴呆症可能会成为21世纪的一大祸害。痴呆症的病因包括阿尔茨海默病、脑血管疾病，以及诸如额颞叶痴呆或路易体痴呆等鲜为人知的病症。神经炎症可能通过炎症机制杀伤神经元，在痴呆症的发病机制中发挥重要作用。神经炎症在阿尔茨海默病中的这种作用已有充分记载，并且它可能在其他类型的痴呆症中也起作用。活性氧（ROS）在炎症性组织破坏中起关键作用。吞噬细胞NADPH氧化酶NOX2是研究得最为透彻的ROS生成系统。在中枢神经系统中，它在小胶质细胞中表达，在神经元中的表达程度较低。确实，有新出现的实验证据表明NOX2在阿尔茨海默病和脑血管疾病中发挥作用。最近，已发现六种与NOX2具有同源性的新型ROS生成NADPH氧化酶。其中几种也在中枢神经系统中表达。在本文中，我们推测NOX型NADPH氧化酶在炎症性神经元丢失中发挥作用。我们回顾了目前可用的证据，并表明NOX型NADPH氧化酶可能成为治疗和预防痴呆症的有前景的药理学靶点。
