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在Aβ42转基因果蝇模型中，Drp1的外源性表达在阿尔茨海默病中发挥神经保护作用。

Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model.

作者信息

Lv Fengshou, Yang Xiaopeng, Cui Chuanju, Su Chunhe

机构信息

Department of Pathology, Henan Medical College, Zhengzhou, China.

Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

PLoS One. 2017 May 22;12(5):e0176183. doi: 10.1371/journal.pone.0176183. eCollection 2017.

DOI:10.1371/journal.pone.0176183
PMID:28531191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5439651/
Abstract

BACKGROUND

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson's disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila.

METHODS

Elav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter. The effects of Drp1 on the lifespan, motor ability and neuronal degeneration of the transgenic Drosophila were explored by over-expressing Drp1 in the Aβ42 transgenic Drosophila. ATP levels in the brain tissues of Aβ42 transgenic Drosophila were detected using high performance liquid chromatography (HPLC).

RESULTS

Exogenous expression of Drp1 promoted crawling ability, reduced the levels of ATP in Drosophila brain and suppressed the neuronal degeneration.

CONCLUSION

The protective effect of Drp1 on the Aβ42 transgenic Drosophila was achieved by protecting the mitochondrial function, suggesting that Drp1 may be a potential therapeutic strategies for AD.

摘要

背景

阿尔茨海默病（AD）是最常见的神经退行性疾病之一。最近的研究表明，线粒体功能障碍是AD的一个致病因素。动力相关蛋白1（Drp1）作为线粒体分裂的调节因子，对帕金森病具有神经保护作用。在本研究中，我们探究了Drp1对Aβ42转基因果蝇的影响及其机制。

方法

利用Elav-gal4启动子构建Elav-gal4/UAS>Aβ42转基因果蝇模型。通过在Aβ42转基因果蝇中过表达Drp1，探讨Drp1对转基因果蝇寿命、运动能力和神经元变性的影响。使用高效液相色谱法（HPLC）检测Aβ42转基因果蝇脑组织中的ATP水平。

结果

Drp1的外源表达促进了果蝇的爬行能力，降低了果蝇脑中ATP水平，并抑制了神经元变性。

结论

Drp1对Aβ42转基因果蝇的保护作用是通过保护线粒体功能实现的，这表明Drp1可能是AD的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/4c8a7f97b95b/pone.0176183.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/b106c00ea36d/pone.0176183.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/6a71c3a4c27e/pone.0176183.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/3d3a16c9a141/pone.0176183.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/4c8a7f97b95b/pone.0176183.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/b106c00ea36d/pone.0176183.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/6a71c3a4c27e/pone.0176183.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/3d3a16c9a141/pone.0176183.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f041/5439651/4c8a7f97b95b/pone.0176183.g004.jpg

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