Reducing acetylated tau is neuroprotective in brain injury. Academic Article uri icon

Overview

abstract

  • 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.

authors

publication date

  • April 13, 2021

Research

keywords

  • Alzheimer Disease
  • Brain Injuries, Traumatic
  • Neuroprotection
  • tau Proteins

Identity

PubMed Central ID

  • PMC8491234

Scopus Document Identifier

  • 85104992839

Digital Object Identifier (DOI)

  • 10.1089/neu.2017.5182

PubMed ID

  • 33852912

Additional Document Info

volume

  • 184

issue

  • 10