Tau and amyloid beta differentially affect the innate immune genes expression in Drosophila models of Alzheimer's disease and β-D Mannuronic acid (M2000) modulates the dysregulation
Tau and amyloid beta differentially affect the innate immune genes expression in Drosophila models of Alzheimer's disease and β-D Mannuronic acid (M2000) modulates the dysregulation
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DOI：
10.1016/j.gene.2021.145972
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发表时间：
2021-10-11
期刊：
影响因子：
3.5
通讯作者：
Mirshafiey, Abbas
中科院分区：
文献类型：
--
作者：
Barati, Anis;Masoudi, Raheleh;Mirshafiey, Abbas
阿尔茨海默病（Alzheimer's disease，AD）是痴呆症最常见的病因，神经炎症被认为是主要的病因之一。本研究的目的是评估A β 42和tau在AD果蝇模型中的炎症通路中的独立作用，并研究M2000作为新型NSAID在这些果蝇中的潜在调节作用。在M2000处理组和未处理组中评价了Relish、NF-κ B的直向同源物、抗菌肽（AMP）（包括attacin A、cknericin B和作为ROS介体的双氧化酶（Duox））的表达水平，随后进行脑组织学分析以评估神经变性的程度。还在体外研究了M2000（β-D甘露糖醛酸）对tau蛋白聚集的潜在抑制作用。结果表明，在老年和AD果蝇模型中，Duox、AMPs及其转录因子的表达均显著增加，这与AD果蝇模型脑切片中空泡数目的增加相一致。有趣的是，M2000治疗显示所有神经变性指数显著降低;体内和抗聚集特性;体外。研究结果表明，M2000有潜力成为AD治疗剂。
Alzheimer's disease (AD) is the most common cause of dementia and neuroinflammation is considered as one of the main culprits. The aim of this study was to evaluate the independent role of A beta 42 and tau on the inflammatory pathway in the Drosophila models of AD and investigating the potential modulating effect of M2000 as a novel NSAIDs in those flies. The expression levels of relish, orthologs of NF-kappa B, antimicrobial peptide (AMP) including attacin A, cknericin B and a dual oxidase (Duox) as a ROS mediator, were evaluated in both M2000 treated and untreated groups followed by brain histology analysis to assess the extent of neurodegeneration. The potential inhibitory role of M2000 (beta-D Mannuronic acid) on the aggregation of tau protein was also investigated in vitro. According to the result, there was a significant induction of Duox, AMPs and its transcription factor expression in both aged and Drosophila models of AD which was in accordance with the increase in the number of vacuoles in the brain section of Drosophila models of AD. Interestingly M2000 treatment revealed a significant reduction in all neurodegeneration indexes; in vivo and anti-aggregating property; in vitro. Findings suggest that M2000 has potential to be an AD therapeutic agent.