| First Author | Seward ME | Year | 2013 |
| Journal | J Cell Sci | Volume | 126 |
| Issue | Pt 5 | Pages | 1278-86 |
| PubMed ID | 23345405 | Mgi Jnum | J:200462 |
| Mgi Id | MGI:5508691 | Doi | 10.1242/jcs.1125880 |
| Citation | Seward ME, et al. (2013) Amyloid-beta signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease. J Cell Sci 126(Pt 5):1278-86 |
| abstractText | Normally post-mitotic neurons that aberrantly re-enter the cell cycle without dividing account for a substantial fraction of the neurons that die in Alzheimer's disease (AD). We now report that this ectopic cell cycle re-entry (CCR) requires soluble amyloid-beta (Abeta) and tau, the respective building blocks of the insoluble plaques and tangles that accumulate in AD brain. Exposure of cultured wild type (WT) neurons to Abeta oligomers caused CCR and activation of the non-receptor tyrosine kinase, fyn, the cAMP-regulated protein kinase A and calcium-calmodulin kinase II, which respectively phosphorylated tau on Y18, S409 and S416. In tau knockout (KO) neurons, Abeta oligomers activated all three kinases, but failed to induce CCR. Expression of WT, but not Y18F, S409A or S416A tau restored CCR in tau KO neurons. Tau-dependent CCR was also observed in vivo in an AD mouse model. CCR, a seminal step in AD pathogenesis, therefore requires signaling from Abeta through tau independently of their incorporation into plaques and tangles. |
