典型文献
Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model
文献摘要：
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.
文献关键词：
中图分类号：
作者姓名：
Zhen-Dong Sun;Jia-Xin Hu;Jia-Rui Wu;Bing Zhou;Yun-Peng Huang
作者机构：
Key Laboratory of Systems Health Science of Zhejiang Province,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou,Zhejiang Province, China;State Key Laboratory of Membrane Biology,School of Life Sciences,Tsinghua University,Beijing,China
文献出处：
引用格式：
[1]Zhen-Dong Sun;Jia-Xin Hu;Jia-Rui Wu;Bing Zhou;Yun-Peng Huang-.Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model)[J].中国神经再生研究（英文版）,2022(10):2286-2292
A类：
Toxicities,hypophosphorylated,dNep1,dNep3,dMmp2,dNep4,dIDE
B类：
amyloid,beta,tau,protein,are,reciprocally,enhanced,Drosophila,Extracellular,aggregation,intracellular,tangles,two,major,pathogenic,hallmarks,critical,factors,Alzheimer,disease,linear,interaction,between,has,been,characterized,several,models,induces,hyperphosphorylation,through,complex,mechanism,however,master,regulators,involved,this,process,still,unclear,In,our,study,melanogaster,found,that,regulated,toxicity,by,activating,Jun,terminal,kinase,Importantly,was,dependent,flies,were,insulated,against,induced,Strikingly,accumulation,interfered,degradation,correlated,reduction,expression,genes,encoding,degrading,enzymes,including,Our,results,indicate,work,synergistically,further,accelerate,progression,may,considered,combined,target,future,development,therapeutics
AB值：
0.606433
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