. Nitrosylation of GAPDH augments pathological tau acetylation upon exposure to amyloid-β. Sci Signal. 2018 Mar 20;11(522) PubMed.


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  1. The proposed signaling cascade—Aβ1-42 induces nitrosylation of GAPDH, which activates p300-mediated tau acetylation on one hand, and inhibits SIRT1-mediated tau deacetylation on the other—provides an interesting mechanism on how Aβ might induce pathogenic tau acetylation. These findings are consistent with our previous studies in which we showed that tau acetylation is elevated in mice overexpressing human APP with Swedish and Indiana mutation (Tracy et al., 2016).

    The in vivo effects induced by the inhibitor of nitrosylation of GAPDH in Aβ–injected mice are quite promising. However, since this study was focused on one axis in the NO signaling network and looked at only one acetylation site (K280) of tau, one cannot rule out possible contributions by other nitrosylated or acetylated/de-acetylated proteins. It would be interesting to further dissect how Aβ triggers such nitrosative stress, and if the same regulatory mechanism applies to other pathogenic proteins in AD and other neurodegenerative diseases.

    — Xu Chen is a co-author of this comment


    . Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss. Neuron. 2016 Apr 20;90(2):245-60. Epub 2016 Mar 31 PubMed.

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