| First Author | Ittner A | Year | 2016 |
| Journal | Science | Volume | 354 |
| Issue | 6314 | Pages | 904-908 |
| PubMed ID | 27856911 | Mgi Jnum | J:237200 |
| Mgi Id | MGI:5811690 | Doi | 10.1126/science.aah6205 |
| Citation | Ittner A, et al. (2016) Site-specific phosphorylation of tau inhibits amyloid-beta toxicity in Alzheimer's mice. Science 354(6314):904-908 |
| abstractText | Amyloid-beta (Abeta) toxicity in Alzheimer's disease (AD) is considered to be mediated by phosphorylated tau protein. In contrast, we found that, at least in early disease, site-specific phosphorylation of tau inhibited Abeta toxicity. This specific tau phosphorylation was mediated by the neuronal p38 mitogen-activated protein kinase p38gamma and interfered with postsynaptic excitotoxic signaling complexes engaged by Abeta. Accordingly, depletion of p38gamma exacerbated neuronal circuit aberrations, cognitive deficits, and premature lethality in a mouse model of AD, whereas increasing the activity of p38gamma abolished these deficits. Furthermore, mimicking site-specific tau phosphorylation alleviated Abeta-induced neuronal death and offered protection from excitotoxicity. Our work provides insights into postsynaptic processes in AD pathogenesis and challenges a purely pathogenic role of tau phosphorylation in neuronal toxicity. |
