The distinctive role of tau and amyloid beta in mitochondrial dysfunction through alteration in Mfn2 and Drp1 mRNA Levels: A comparative study in Drosophila melanogaster
The distinctive role of tau and amyloid beta in mitochondrial dysfunction through alteration in Mfn2 and Drp1 mRNA Levels: A comparative study in Drosophila melanogaster
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DOI：
10.1016/j.gene.2020.144854
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发表时间：
2020-09-05
期刊：
影响因子：
3.5
通讯作者：
Haddadi, Mohammad
中科院分区：
文献类型：
--
作者：
Abtahi, Seyedeh Leila;Masoudi, Raheleh;Haddadi, Mohammad
阿尔茨海默病（AD）是最常见的神经退行性疾病之一。A β 42的聚集和过度磷酸化的mu是AD的两个主要标志。不同形式的tau（可溶性或过度磷酸化）或A β是否是在AD中观察到的事件的罪魁祸首仍在研究中。在这里，我们研究了野生型，容易过度磷酸化和过度磷酸化的亩，也A β 42肽对脑抗氧化防御系统和两个线粒体基因，Marf（同源于人类MFN2）和Drp1参与转基因果蝇的线粒体动力学的影响。AD是一种与年龄相关的疾病。因此，抗氧化剂的活性，CAT，SOD，GSH水平和mRNA水平的Marf和Drp1的果蝇寿命的不同时间点进行了评估。在任何时间点，在所有转基因果蝇中均观察到认知功能和抗氧化活性降低。对眼睛表型的最大和最小影响分别由过度磷酸化的mu和A β 42产生。此外，最显着的变化，在Marf和Drp1 mRNA水平的转基因果蝇表达过度磷酸化亩时，泛神经元表达的转基因被应用。然而，当致病基因表达仅限于蘑菇体时，Marf和Drp1 mRNA水平的改变分别在tau（wT）和tau（E14）转基因果蝇中更为突出。总之，尽管不同类型的tau和A β 42引起抗氧化剂缺乏，但似乎mu对眼睛表型和线粒体基因调控（Marf和Drp1）产生更大的毒性作用。此外，当Aji或各种形式的tau表达时，线粒体基因失调似乎涉及不同的机制。
Alzheimer's disease (AD) is one of the most common forms of neurodegenerative diseases. Aggregation of A beta 42 and hyperphosphorylated mu are two major hallmarks of AD. Whether different forms of tau (soluble or hyperphosphorylated) or A beta are the main culprit in the events observed in AD is still under investigation. Here, we examined the effect of wild-type, prone to hyperphosphorylation and hyperphosphorylated mu, and also A beta 42 peptide on the brain antioxidant defense system and two mitochondrial genes, Marf (homologous to human MFN2) and Drp1 involved in mitochondrial dynamics in transgenic Drosophila melanogaster. AD is an age associated disease. Therefore, the activity of antioxidant agents, CAT, SOD, and GSH levels and the mRNA levels of Marf and Drp1 were assessed in different time points of the flies lifespan. Reduction in cognitive function and antioxidant activity was observed in all transgenic flies at any time point. The most and the least effect on the eye phenotype was exerted by hyperphosphorylated mu and A beta 42, respectively. In addition, the most remarkable alteration in Marf and Drp1 mRNA levels was observed in transgenic flies expressing hyperphosphorylated mu when pan neuronal expression of transgenes was applied. However, when the disease causing gene expression was confined to the mushroom body, Marf and Drp1 mRNA levels alteration was more prominent in tau(wT) and tau(E14) transgenic flies, respectively. In conclusion, in spite of antioxidant deficiency caused by different types of tau and A beta 42, it seems that mu exerts more toxic effect on the eye phenotype and mitochondrial genes regulation (Marf and Drp1). Moreover, different mechanisms seem to be involved in mitochondrial genes dysregulation when Aji or various forms of tau are expressed.