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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 Aβ42 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-κB, antimicrobial peptide (AMP) including attacin A, diptericin 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 (β-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 …