The Angiotensin-Converting Enzyme Inhibitor Lisinopril Mitigates Memory and Motor Deficits in a Drosophila Model of Alzheimer's Disease.
The Angiotensin-Converting Enzyme Inhibitor Lisinopril Mitigates Memory and Motor Deficits in a Drosophila Model of Alzheimer's Disease.
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血管紧张素转换酶抑制剂赖诺普利在阿尔茨海默氏病的果蝇模型中减轻记忆力和运动缺陷。
DOI：
10.3390/pathophysiology28020020
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发表时间：
2021-06-18
期刊：
影响因子：
--
通讯作者：
Jumbo-Lucioni P
中科院分区：
文献类型：
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作者：
Thomas J;Smith H;Smith CA;Coward L;Gorman G;De Luca M;Jumbo-Lucioni P
据报道，血管紧张素转换酶抑制剂（ACEis）的使用可减轻阿尔茨海默病（AD）患者认知能力下降的症状。然而，ACEis对AD症状的保护作用仍存在争议。在这里，我们的目的是确定口服ACEi赖诺普利是否对过表达人淀粉样蛋白前体蛋白和神经元中人β位点app切割酶的黑胃果蝇AD模型的认知和身体功能有有益影响。我们发现，与对照蝇相比，年轻的AD蝇在学习、记忆和攀爬能力方面有显著的损害。在对色氨酸代谢的犬尿氨酸途径进行评估后，我们还发现AD果蝇头部神经毒性3-羟基犬尿氨酸（3-HK）水平增加了约30倍。此外，与对照蝇相比，AD蝇在其肌肉丰富的胸部中具有明显更高水平的活性氧（ROS）过氧化氢。赖诺普利可显著改善阿尔茨海默病果蝇的学习记忆和攀爬能力缺陷。赖诺普利对身体功能的积极影响可能部分地解释为赖诺普利喂养的AD果蝇胸腔中ROS水平的显著降低。赖诺普利不影响3-HK水平。总之，我们的研究结果为ACEis在临床前AD模型中的治疗潜力提供了新颖和相关的见解。
The use of angiotensin-converting enzyme inhibitors (ACEis) has been reported to reduce symptoms of cognitive decline in patients with Alzheimer’s disease (AD). Yet, the protective role of ACEis against AD symptoms is still controversial. Here, we aimed at determining whether oral treatment with the ACEi lisinopril has beneficial effects on cognitive and physical functions in a Drosophila melanogaster model of AD that overexpresses the human amyloid precursor protein and the human β-site APP-cleaving enzyme in neurons. We found a significant impairment in learning and memory as well as in climbing ability in young AD flies compared to control flies. After evaluation of the kynurenine pathway of tryptophan metabolism, we also found that AD flies displayed a >30-fold increase in the levels of the neurotoxic 3-hydroxykynurenine (3-HK) in their heads. Furthermore, compared to control flies, AD flies had significantly higher levels of the reactive oxygen species (ROS) hydrogen peroxide in their muscle-enriched thoraces. Lisinopril significantly improved deficits in learning and memory and climbing ability in AD flies. The positive impact of lisinopril on physical function might be, in part, explained by a significant reduction in ROS levels in the thoraces of the lisinopril-fed AD flies. However, lisinopril did not affect the levels of 3-HK. In conclusion, our findings provide novel and relevant insights into the therapeutic potential of ACEis in a preclinical AD model.
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影响因子：
6.1
作者：
Braidy N;Grant R
通讯作者：
Grant R
影响因子：
4.7
作者：
Fournier, David;Luft, Friedrich C.;Bader, Michael;Ganten, Detlev;Andrade-Navarro, Miguel A.
通讯作者：
Andrade-Navarro, Miguel A.
影响因子：
5.2
作者：
Campbell DJ
通讯作者：
Campbell DJ
影响因子：
14
作者：
Brookmeyer, Ron;Johnson, Elizabeth;Arrighi, H. Michael
通讯作者：
Arrighi, H. Michael
影响因子：
14
作者：
通讯作者：
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