Reducing acetylated tau is neuroprotective in brain injury

Shin, Min-Kyoo; Vazquez-Rosa, Edwin; Koh, Yeojung; Dhar, Matasha; Chaubey, Kalyani; Cintron-Perez, Coral J.; Barker, Sarah; Miller, Emiko; Franke, Kathryn; Noterman, Maria F.; Seth, Divya; Allen, Rachael S.; Motz, Cara T.; Rao, Sriganesh Ramachandra; Skelton, Lara A.; Pardue, Machelle T.; Fliesler, Steven J.; Wang, Chao; Tracy, Tara E.; Gan, Li; Liebl, Daniel J.; Savarraj, Jude P. J.; Torres, Glenda L.; Ahnstedt, Hilda; McCullough, Louise D.; Kitagawa, Ryan S.; Choi, H. Alex; Zhang, Pengyue; Hou, Yuan; Chiang, Chien-Wei; Li, Lang; Ortiz, Francisco; Kilgore, Jessica A.; Williams, Noelle S.; Whitehair, Victoria C.; Gefen, Tamar; Flanagan, Margaret E.; Stamler, Jonathan S.; Jain, Mukesh K.; Kraus, Allison; Cheng, Feixiong; Reynolds, James D.; Pieper, Andrew A. ✉

Angol nyelvű Tudományos Sokszerzős vagy csoportos szerzőségű szakcikk (Folyóiratcikk)
Megjelent: CELL 0092-8674 1097-4172 184 (10) pp. 2715-271+ 2021
  • SJR Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous): D1
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.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2021-12-09 05:21