Reference - Detail
| RRC ID | 6620 |
|---|---|
| Author | Sahara N, Murayama M, Lee B, Park JM, Lagalwar S, Binder LI, Takashima A. |
| Title | Active c-jun N-terminal kinase induces caspase cleavage of tau and additional phosphorylation by GSK-3beta is required for tau aggregation. |
| Journal | Eur J Neurosci |
| Abstract |
Neurofibrillary tangles (NFTs), comprising human intracellular microtubule-associated protein tau, are one of the hallmarks of tauopathies, including Alzheimer's disease. Recently, a report that caspase-cleaved tau is present in NFTs has led to the hypothesis that the mechanisms underlying NFT formation may involve the apoptosis cascade. Here, we show that adenoviral infection of tau into COS-7 cells induces activation of c-jun N-terminal kinase (JNK), followed by excessive phosphorylation of tau and its cleavage by caspase. However, JNK activation alone was insufficient to induce sodium dodecyl sulfate (SDS)-insoluble tau aggregation and additional phosphorylation by GSK-3beta was required. In SH-SY5Y neuroblastoma cells, overexpression of active JNK and GSK-3beta increased caspase-3 activation and cytotoxicity more than overexpression of tau alone. Taken together, these results indicate that, although JNK activation may be a primary inducing factor, further phosphorylation of tau is required for neuronal death and NFT formation in neurodegenerative diseases, including those characterized by tauopathy. |
| Volume | 27(11) |
| Pages | 2897-906 |
| Published | 2008-6-1 |
| DOI | 10.1111/j.1460-9568.2008.06258.x |
| PII | EJN6258 |
| PMID | 18540881 |
| MeSH | Alzheimer Disease / metabolism Alzheimer Disease / pathology Alzheimer Disease / physiopathology Animals Brain / metabolism Brain / pathology Brain / physiopathology COS Cells Caspase 3 / metabolism Caspases / metabolism* Cell Line, Tumor Chlorocebus aethiops Enzyme Activation / genetics Genetic Vectors / genetics Glycogen Synthase Kinase 3 / metabolism* Glycogen Synthase Kinase 3 beta Humans JNK Mitogen-Activated Protein Kinases / metabolism* Mice Neurofibrillary Tangles / metabolism* Neurofibrillary Tangles / pathology Neurons / metabolism* Neurons / pathology Phosphorylation Sodium Dodecyl Sulfate / pharmacology Surface-Active Agents / pharmacology Transfection tau Proteins / genetics tau Proteins / metabolism* |
| IF | 2.74 |
| Times Cited | 21 |
| WOS Category | CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | COS-7(RCB0539) |