| First Author | Shin MK | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 10 | Pages | 2715-2732.e23 |
| PubMed ID | 33852912 | Mgi Jnum | J:306960 |
| Mgi Id | MGI:6712864 | Doi | 10.1016/j.cell.2021.03.032 |
| Citation | Shin MK, et al. (2021) Reducing acetylated tau is neuroprotective in brain injury. Cell 184(10):2715-2732.e23 |
| abstractText | Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI. |
