Susceptibility to GSK3β-induced tau phosphorylation differs between the young and aged hippocampus after Wnt signaling inhibition
| Autor: | Pamela Salcedo-Tello, Clorinda Arias, Karina Hernández-Ortega |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Aging Tau protein Down-Regulation tau Proteins macromolecular substances Biology environment and public health Hippocampus Dephosphorylation Glycogen Synthase Kinase 3 Organ Culture Techniques GSK-3 Internal medicine medicine Animals Genetic Predisposition to Disease Phosphorylation Rats Wistar GSK3B Wnt Signaling Pathway Glycogen Synthase Kinase 3 beta General Neuroscience Wnt signaling pathway LRP5 Neural Inhibition General Medicine Protein phosphatase 2 Rats Wnt Proteins enzymes and coenzymes (carbohydrates) Psychiatry and Mental health Clinical Psychology Endocrinology biology.protein Intercellular Signaling Peptides and Proteins Geriatrics and Gerontology |
| Zdroj: | Journal of Alzheimer's disease : JAD. 39(4) |
| ISSN: | 1875-8908 |
| Popis: | The abnormal phosphorylation of the microtubule-associated protein tau is a prominent aspect of Alzheimer's disease (AD). Considerable evidence suggests that glycogen synthase kinase 3β (GSK3β) and the protein phosphatase 2A (PP2A) are involved in normal and pathological tau phosphorylation. However, the mechanisms underlying a shift of the phosphorylation/dephosphorylation balance that leads to abnormal tau phosphorylation remains unknown. The canonical Wnt pathway negatively regulates GSK3β activity, and this signaling pathway has also been found to be dysregulated in the AD brain. Here, we report that the Wnt antagonist Dkk-1 selectively increases tau phosphorylation in the hippocampus of aged rats at Ser199/202, Ser396/404, and Ser214 sites. In the aged hippocampus, the inhibition of Wnt signaling is also accompanied by reduced PP2A activity. This study suggests that aging promotes tau hyperphosphorylation after Wnt inhibition, due to an imbalance between GSK3β and PP2A activities. |
| Databáze: | OpenAIRE |
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