【摘 要】
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Extracellular aggregation of amyloid-beta (Aβ) and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer\'s disease. A linear interaction between Aβ and tau protein has been characterized in several models. Aβ in
【机 构】
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Key Laboratory of Systems Health Science of Zhejiang Province,Hangzhou Institute for Advanced Study,
论文部分内容阅读
Extracellular aggregation of amyloid-beta (Aβ) and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer\'s disease. A linear interaction between Aβ and tau protein has been characterized in several models. Aβ induces tau hyperphosphorylation through a complex mechanism; however, the master regulators involved in this linear process are still unclear. In our study with Drosophila melanogaster, we found that Aβ regulated tau hyperphosphorylation and toxicity by activating c-Jun N-terminal kinase. Importantly, Aβ toxicity was dependent on tau hyperphosphorylation, and flies with hypophosphorylated tau were insulated against Aβ-induced toxicity. Strikingly, tau accumulation reciprocally interfered with Aβ degradation and correlated with the reduction in mRNA expression of genes encoding Aβ-degrading enzymes, including dNep1, dNep3, dMmp2, dNep4, and dIDE. Our results indicate that Aβ and tau protein work synergistically to further accelerate Alzheimer\'s disease progression and may be considered as a combined target for future development of Alzheimer\'s disease therapeutics.
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