Unknown

Dataset Information

0

Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model.


ABSTRACT: 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.

SUBMITTER: Lasagna-Reeves CA 

PROVIDER: S-EPMC5745060 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


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-bas  ...[more]

Similar Datasets

| S-EPMC5413341 | biostudies-literature
| S-EPMC5792300 | biostudies-literature
| S-EPMC6223064 | biostudies-literature
| S-EPMC3739054 | biostudies-literature
| S-EPMC9307951 | biostudies-literature
| S-EPMC11354494 | biostudies-literature
| S-EPMC5641217 | biostudies-literature
| S-EPMC9641281 | biostudies-literature
| S-EPMC9005658 | biostudies-literature
| S-EPMC5757517 | biostudies-literature