盐酸多奈哌齐对转基因表达人Aβ-42的影响。
Effect of donepezil hydrochloride on the transgenic expressing human Aβ-42.
作者信息
Siddique Yasir Hasan, Naz Falaq, Varshney Himanshi, Idrisi Mantasha, Shahid M
机构信息
Drosophila Transgenic Laboratory, Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.
Department of Chemistry, Faculty of Sciences, Aligarh Muslim University, Aligarh, India.
出版信息
Int J Neurosci. 2024 Nov;134(11):1293-1308. doi: 10.1080/00207454.2023.2262109. Epub 2023 Nov 21.
AIM
In the present study, the effect of donepezil hydrochloride was studied on the transgenic expressing human amyloid beta-42 in the neurons.
METHODS
Donepezil hydrochloride at final concentration of 0.1, 1 and 10 mM was mixed in the diet and the flies expressing human amyloid beta-42 under Upstream Activation Sequence control (Alzheimer Disease [AD] flies) were allowed to feed on it for 30 days.
RESULTS
The AD flies exposed to various doses of Donepezil hydrochloride showed a dose dependent significant delay in the loss of climbing ability, increase in activity, reduction in the oxidative stress and apoptotic markers. A significant improvement was also observed in cognitive parameters. A dose dependent significant reduction in the activity of acetylcholinesterase was also observed. The docking studies suggest the positive interaction between donepezil, amyloid beta-42 and acetylcholinesterase. The results obtained from immunohistochemistry also showed a dose dependent significant reduction in the amyloid beta-42 aggregates.
CONCLUSION
The results suggest that donepezil hydrochloride is potent enough to reduce the AD symptoms being mimicked in transgenic flies.
目的
在本研究中，研究了盐酸多奈哌齐对在神经元中表达人淀粉样β-42的转基因果蝇的影响。
方法
将终浓度为0.1、1和10 mM的盐酸多奈哌齐混入食物中，让在上游激活序列控制下表达人淀粉样β-42的果蝇（阿尔茨海默病[AD]果蝇）取食30天。
结果
暴露于不同剂量盐酸多奈哌齐的AD果蝇在攀爬能力丧失方面出现剂量依赖性显著延迟，活动增加，氧化应激和凋亡标志物减少。在认知参数方面也观察到显著改善。还观察到乙酰胆碱酯酶活性呈剂量依赖性显著降低。对接研究表明多奈哌齐、淀粉样β-42和乙酰胆碱酯酶之间存在正向相互作用。免疫组织化学结果也显示淀粉样β-42聚集体呈剂量依赖性显著减少。
结论
结果表明盐酸多奈哌齐有足够的效力减轻转基因果蝇模拟的AD症状。
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