Praticò Domenico
Department of Pharmacology, Temple University, School of Medicine, Philadelphia, PA 19140, USA.
Biochim Biophys Acta. 2010 Aug;1801(8):930-3. doi: 10.1016/j.bbalip.2010.01.009. Epub 2010 Jan 29.
In its sporadic form Alzheimer's disease (AD) results from a combination of genetic and environmental risk factors with abnormal oxidative reactions, which result in free radical mediated injury of the brain. Isoprostanes are oxidized lipids formed by a free radical mediated mechanism, which in recent years have emerged as a reliable and sensitive marker of lipid peroxidation and oxidative stress. Consistent data show that they are increased in the brain of human AD as well as AD animal models. Besides their role as biomarkers, isoprostanes possess important biological effects, functioning as mediators of the cellular response to oxidative stress within the CNS. Recent evidence indicates that these lipid oxidation products, by activating the thromboxane receptor system, mediate the pro-amyloidotic neuronal response to oxidative stress in an experimental model of AD. This novel observation has important clinical implication, since pharmacologic modulation of the TP receptor system by selective antagonists, some of which are already available, could represent a novel therapeutic opportunity for AD as disease-modifying agents.
散发性阿尔茨海默病（AD）由遗传和环境风险因素与异常氧化反应共同作用导致，这些异常氧化反应会引发自由基介导的脑损伤。异前列腺素是通过自由基介导机制形成的氧化脂质，近年来已成为脂质过氧化和氧化应激的可靠且敏感的标志物。一致的数据表明，它们在人类AD大脑以及AD动物模型中均有所增加。除了作为生物标志物的作用外，异前列腺素还具有重要的生物学效应，可作为中枢神经系统内细胞对氧化应激反应的介质。最近的证据表明，在AD实验模型中，这些脂质氧化产物通过激活血栓素受体系统，介导促淀粉样蛋白生成的神经元对氧化应激的反应。这一新发现具有重要的临床意义，因为通过选择性拮抗剂对TP受体系统进行药理调节（其中一些拮抗剂已可获得），可能为AD提供一种作为疾病修饰药物的新治疗机会。
