p(MGI:Mapt, pmod(Ac, Lys, 280)) positiveCorrelation p(MGI:Gapdh, pmod(NO))

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PubMed:29559585

We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42), a peptide that is also implicated in AD. An increased abundance of NO facilitated the S-nitrosylation (SNO) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). S-nitrosylated GAPDH (GAPDH-SNO) promoted the acetylation and activation of the acetyltransferase p300 and facilitated the nitrosylation and inactivation of the deacetylase sirtuin 1 (SIRT1). The abundance of GAPDH-SNO was increased in postmortem brain samples from AD patients. Preventing the increase in GAPDH-SNO abundance in both cultured neurons and mice, either by overexpression of the nitrosylation mutant of GAPDH (GAPDH C150S) or by treatment with the GAPDH nitrosylation inhibitor CGP3466B (also known as omigapil), abrogated Aβ1-42-induced tau acetylation, memory impairment, and locomotor dysfunction in mice, suggesting that this drug might be repurposed to treat patients with AD.

Related Edges 9

• a(CHEBI:"nitric oxide") increases p(MGI:Gapdh, pmod(NO))
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• act(p(MGI:Ep300)) positiveCorrelation p(MGI:Sirt1, pmod(NO))
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• p(MGI:Gapdh, pmod(NO)) positiveCorrelation p(MGI:Mapt, pmod(Ac, Lys, 280))
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