Many neurodegenerative proteinopathies share a common pathogenic mechanism: the abnormal accumulation of disease-related proteins. As growing evidence indicates that reducing the steady-state levels of disease-causing proteins mitigates neurodegeneration in animal models, we developed a strategy to screen for genes that decrease the levels of tau, whose accumulation contributes to the pathology of both Alzheimer disease (AD) and progressive supranuclear palsy (PSP). Integrating parallel cell-based and Drosophila genetic screens, we discovered that tau levels are regulated by Nuak1, an AMPK-related kinase. Nuak1 stabilizes tau by phosphorylation specifically at Ser356. Inhibition of Nuak1 in fruit flies suppressed neurodegeneration in tau-expressing Drosophila, and Nuak1 haploinsufficiency rescued the phenotypes of a tauopathy mouse model. These results demonstrate that decreasing total tau levels is a valid strategy for mitigating tau-related neurodegeneration and reveal Nuak1 to be a novel therapeutic entry point for tauopathies.
Pubmed ID: 27720485 RIS Download
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This unknown targets IgG (H+L)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Vinculin antibody produced in mouse
View all literature mentionsThis polyclonal targets ARK5 antibody
View all literature mentionsThis monoclonal targets Tau Phospho (pS262)
View all literature mentionsThis monoclonal targets Tau Phospho (pS356)
View all literature mentionsThis monoclonal targets Tau
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsMus musculus with name B6.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J from IMSR.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal targets ARK5 antibody
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsMus musculus with name B6.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J from IMSR.
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Vinculin antibody produced in mouse
View all literature mentionsThis monoclonal targets Tau Phospho (pS262)
View all literature mentionsThis monoclonal targets Tau Phospho (pS356)
View all literature mentionsThis monoclonal targets Tau
View all literature mentions