Reducing acetylated tau is neuroprotective in brain injury.
Cell
; 184(10): 2715-2732.e23, 2021 05 13.
Article
em En
| MEDLINE
| ID: mdl-33852912
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas tau
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Doença de Alzheimer
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Neuroproteção
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Lesões Encefálicas Traumáticas
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell
Ano de publicação:
2021
Tipo de documento:
Article