Effect of ACE inhibitor on ACE gene and tau protein expression in neurons.

• Main Authors: I Chien, 簡薏
• Other Authors: Shyh-Jong Wu
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/q2q7qu

碩士 === 高雄醫學大學 === 醫學檢驗生物技術學研究所 === 102 === Alzheimer''s disease (AD) is a neurodegenerative disease with progressive loss of neuronal functions, which in turn results in memory deficits, cognitive deterioration, and impaired motor coordination. The growing aged population has led to an increased prevalence of AD. However, there is no effective treatment to halt the progression or prevent the onset of AD. Previous studies have indicated angiotensin-converting enzyme (ACE) () inhibitor improved the cognitive impairment, but the mechanisms are still unclear. Our previous finding indicated that Alu sequence in human ACE gene possesses a regulatory function on the ACE promoter activity in neurons. Moreover, a previous study indicated that ACE inhibitor enhanced ACE gene expression. We aimed to investigate the pharmacogenetic effect of ACE inhibitors on ACE I/D polymorphism. We used transient transfection and reporter assay to examine the intracellular ACE signaling pathway in SH-SY5Y cells. We find that lisinopril , a ACE inhibitor, enhances ACE promoter transcriptional activity and that the ACE I/D polymorphism differently responds to lisinopril in regulating ACE promoter activity in neurons. The hyper-phosphorylated tau protein has been one of hallmarks for AD. In this study, we also aimed to investigate whether ACE inhibitors regulate hyper-phosphorylated tau protein in neuron and to observe whether the regulators of phosphorylated tau are affected by ACE inhibitors, including GSK3β (glycogen synthase kinase 3 beta), AKT(protein kinase B), PP2A(protein phosphatase 2A). We find that lisinoplril could decrease the hyper-phosphorylation of tau protein induced by okadaic acid. Our results show ACE inhibitors have pharmacogentic effect on ACE gene and might protect neurodegeneration from hyperphosphorlated of tau protein.