University of lagos.
university of lagos.
Niger J Physiol Sci. 2022 Jun 30;37(1):21-28. doi: 10.54548/njps.v37i1.3.
Parkinson disease (PD) and Alzheimer's disease (AD) are progressive neurodegenerative disorders characterized by loss of selective neurons in discreet part of the brain. The peptide angiotensin II (Ang II) plays significant role in hippocampal and striatal neurons degeneration through the generation of reactive oxygen species. Blockade of the angiotensin converting enzyme or ATI receptors provides protection in animal models of neurodegenerative diseases. In the present study, the neuroprotective effect of captopril was investigated in Drosophila melanogaster model using the UAS-GAL4 system to express the synuclein and Aβ42 peptide in the flies' neurons.
The disease causing human Aβ42 peptide or α-syn was expressed pan-neuronally (elav-GAL4) or dopamine neuron (DDC-GAL4) using the UAS-GAL4 system. Flies were either grown in food media with or without captopril (1, 5, or 10µM). This was followed by fecundity, larva motility, negative geotaxis assay (climbing) and lifespan as a measure of neurodegeneration.
Elav-Gal4<Aβ or DDC-GAL4<α-syn flies displayed significant decrease in larva motility when compared with normal control (w1118) which was reversed by the supplementation of the media with captopril (5 or 10 mM) indicative of neuroprotection. Interestingly, supplementation of flies' media with captopril improved climbing activity in Elav-Gal4<Aβ or DDC-GAL4<α-syn flies when compared with vehicle treated only. Moreover, flies grown on captopril caused no significant change in lifespan. Conclusion: Findings from this study confirmed the neuroprotective action of captopril in genetic or familial forms of neurodegeneration.
帕金森病（PD）和阿尔茨海默病（AD）是两种进行性神经退行性疾病，其特征是大脑特定部位选择性神经元的丧失。肽血管紧张素 II（Ang II）通过生成活性氧在海马和纹状体神经元变性中起重要作用。血管紧张素转换酶或 AT1 受体的阻断在神经退行性疾病的动物模型中提供保护。在本研究中，使用 UAS-GAL4 系统在黑腹果蝇模型中研究了卡托普利的神经保护作用，该系统在果蝇神经元中表达突触核蛋白和 Aβ42 肽。
使用 UAS-GAL4 系统，通过泛神经元（elav-GAL4）或多巴胺神经元（DDC-GAL4）表达致病的人 Aβ42 肽或 α-突触核蛋白。果蝇要么在含有或不含有卡托普利（1、5 或 10µM）的食物培养基中生长。随后进行繁殖力、幼虫运动性、负趋地性（攀爬）和寿命作为神经退行性变的衡量标准。
与正常对照（w1118）相比，Elav-Gal4<Aβ 或 DDC-GAL4<α-syn 果蝇的幼虫运动性显著下降，而用卡托普利（5 或 10 mM）补充培养基可逆转这种情况，表明具有神经保护作用。有趣的是，与仅用载体处理的果蝇相比，用卡托普利补充果蝇培养基可改善 Elav-Gal4<Aβ 或 DDC-GAL4<α-syn 果蝇的攀爬活动。此外，在卡托普利上生长的果蝇的寿命没有明显变化。结论：本研究的结果证实了卡托普利在遗传或家族性神经退行性变中的神经保护作用。
