Nitrosylation of GAPDH augments pathological tau acetylation upon exposure to amyloid-β.

ABSTRACT: Acetylation of the microtubule-associated protein tau promotes its polymerization into neurofibrillary tangles that are implicated in the pathology of Alzheimer's disease (AD). The gaseous neurotransmitter nitric oxide (NO) regulates cell signaling through the nitrosylation of proteins. 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-β_1-42 (Aβ_1-42), 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

SUBMITTER: Sen T 

PROVIDER: S-EPMC6371980 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature