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细胞产生的活性氧(ROS)的增加是阿尔茨海默病(AD)患者脑中的重要病理生理特征。实验证据表明抑制脑ROS有益于减慢由淀粉样蛋白-β(Abeta)聚集引发的神经变性过程。血管紧张素II AT1受体是脑ROS的重要来源,并且AD患者的脑血管紧张素转化酶(ACE)水平增加,这种现象可以解释过度的血管紧张素依赖性AT1诱导的ROS产生。因此,科学家们将年龄Tg2576的小鼠作为AD的转基因动物模型并分析了ACE抑制剂对上述动物的神经变性的迹象的影响。全基因组微阵列基因表达谱和生物化学分析表明中枢活性ACE抑制剂卡托普利使过度活跃的AD小鼠的海马ACE正常化。与此同时,通过六个月的卡托普利治疗,神经变性的体征的发展得以延迟。由卡托普利触发的神经保护谱伴随着淀粉样前体蛋白(APP)的淀粉样蛋白形成加工的减少,以及海马ROS的减少,已知其通过增加β-分泌酶和γ-分泌酶的活化来增强Aβ产生。总而言之,科学家们的数据表明ACE抑制剂与广泛使用的心血管药物可以干扰Abeta依赖神经变性的证据。
Increased reactive oxygen species (ROS) produced by cells is an important pathophysiological feature in the brain of patients with Alzheimer’s disease (AD). Experimental evidence suggests that inhibition of brain ROS is beneficial for slowing the neurodegeneration triggered by amyloid-beta (Abeta) aggregation. The angiotensin II AT1 receptor is an important source of brain ROS and the increased levels of cerebrovascular angiotensin converting enzyme (ACE) in AD patients explain the excessive angiotensin-dependent AT1-induced ROS production. Therefore, scientists used age Tg2576 mice as a transgenic animal model of AD and analyzed the effect of ACE inhibitors on the signs of neurodegeneration in these animals. Genome-wide microarray gene expression profiling and biochemical analyzes showed that central active ACE inhibitor captopril normalizes hippocampal ACE in hyperactive AD mice. At the same time, the development of neurodegenerative signs is delayed by six months of captopril treatment. Neuroprotection profiles triggered by captopril are accompanied by a reduction in the amyloidogenic processing of amyloid precursor protein (APP), and a decrease in ROS in the hippocampus, which is known to be mediated by the increase of beta-secretase and gamma-secretase Activation to enhance Aβ production. All in all, scientists’ data suggest that ACE inhibitors and widely used cardiovascular drugs may interfere with the evidence of Abeta-dependent neurodegeneration.