Cystatin C promotes tau protein phosphorylation and causes microtubule instability by inhibiting intracellular turnover of GSK3β in neurons
| Autor: | Jinhai Duan, Xike Qin, Hemant K. Paudel, Yunling Wang, Kristen A. Marcellus |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Tau protein Hyperphosphorylation tau Proteins Microtubules PC12 Cells Pathogenesis 03 medical and health sciences Cellular and Molecular Neuroscience Mice Downregulation and upregulation Microtubule Alzheimer Disease medicine Animals Humans Cystatin C Phosphorylation Molecular Biology Neurons Glycogen Synthase Kinase 3 beta biology Neurodegeneration Cell Biology medicine.disease 3. Good health Cell biology Rats 030104 developmental biology HEK293 Cells Proteolysis biology.protein Protein Processing Post-Translational |
| Zdroj: | Molecular and cellular neurosciences. 89 |
| ISSN: | 1095-9327 |
| Popis: | In Alzheimer's disease (AD) tau protein hyperphosphorylation causes neurofibrillary tangle formation, microtubule instability and neurodegeneration. Determining the mechanism of tau hyperphosphorylation will provide a better understanding of AD pathology. Cystatin C (CysC) is a risk factor for late-onset AD and its level is upregulated in the brains of AD patients. The role of CysC is AD pathogenesis is not known. In this study, we found that CysC level is upregulated in 3xTg-AD mouse brain. We demonstrate that CysC does not affect cellular Aβ production. However, when overexpressed in neuron (NGF-differentiated PC12 cells), CysC inhibits turnover of GSK3β, promotes GSK3β-catalyzed tau phosphorylation at Ser396/404 and causes microtubule instability. Our data provide a novel insight into the role of CysC in AD pathogenesis. |
| Databáze: | OpenAIRE |
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