Garrison Institute on Aging, Department of Neuropsychiatry and Behavioral Sciences, Texas Tech University Health Sciences Center, 3601 4th Street Stop 9424, Lubbock, TX 79430, United States.
Neurobiol Aging. 2010 Jan;31(1):8-16. doi: 10.1016/j.neurobiolaging.2008.03.009. Epub 2008 Apr 28.
Numerous studies demonstrate inflammatory proteins in the brain and microcirculation in Alzheimer's disease (AD) and implicate inflammation in disease pathogenesis. However, emerging literature suggests that neuroinflammation can also be neuroprotective. The chemokine RANTES has been implicated in neurodegenerative diseases including AD. The objectives of this study are to determine the expression of RANTES in AD microvessels, its regulation in endothelial cells and its effects on neuronal survival. Our data show elevated expression of RANTES in the cerebral microcirculation of AD patients. Treatment of neurons in vitro with RANTES results in an increase in cell survival and a neuroprotective effect against the toxicity of thrombin and sodium nitroprusside. Oxidative stress upregulates RANTES expression in rat brain endothelial cells. Developing strategies to augment neuroprotection and diminish inflammatory activation of multifunctional mediators such as RANTES holds promise for the development of novel neuroprotective therapeutics in AD.
大量研究表明，阿尔茨海默病（AD）患者的大脑和微循环中存在炎症蛋白，并提示炎症在疾病发病机制中起作用。然而，新出现的文献表明，神经炎症也可能具有神经保护作用。趋化因子 RANTES 与包括 AD 在内的神经退行性疾病有关。本研究旨在确定 RANTES 在 AD 微血管中的表达情况、其在血管内皮细胞中的调控作用以及对神经元存活的影响。我们的数据显示，AD 患者的大脑微循环中 RANTES 的表达水平升高。体外给予神经元 RANTES 可增加细胞存活，并对凝血酶和硝普钠的毒性产生神经保护作用。氧化应激可上调大鼠脑内皮细胞中 RANTES 的表达。开发增强神经保护和减少多功能介质（如 RANTES）炎症激活的策略，有望为 AD 新型神经保护治疗的发展提供新的思路。
