PMID- 29559585
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20200306
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Print)
IS  - 1945-0877 (Linking)
VI  - 11
IP  - 522
DP  - 2018 Mar 20
TI  - Nitrosylation of GAPDH augments pathological tau acetylation upon exposure to 
      amyloid-beta.
LID - 10.1126/scisignal.aao6765 [doi]
LID - eaao6765
AB  - 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 Lys(280) occurred in the brain tissue in mice and in cultured 
      mouse cortical neurons in response to exposure to amyloid-beta(1-42) (Abeta(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 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 
      Abeta(1-42)-induced tau acetylation, memory impairment, and locomotor dysfunction in 
      mice, suggesting that this drug might be repurposed to treat patients with AD.
CI  - Copyright (c) 2018 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Sen, Tanusree
AU  - Sen T
AUID- ORCID: 0000-0002-8970-7007
AD  - Department of Neurological Surgery, University of Pittsburgh, 200 Lothrop Street, 
      Scaife Hall, Pittsburgh, PA 15213, USA.
FAU - Saha, Pampa
AU  - Saha P
AUID- ORCID: 0000-0002-4926-9081
AD  - Department of Neurological Surgery, University of Pittsburgh, 200 Lothrop Street, 
      Scaife Hall, Pittsburgh, PA 15213, USA.
FAU - Sen, Nilkantha
AU  - Sen N
AUID- ORCID: 0000-0002-8383-8209
AD  - Department of Neurological Surgery, University of Pittsburgh, 200 Lothrop Street, 
      Scaife Hall, Pittsburgh, PA 15213, USA. senn@pitt.edu.
LA  - eng
GR  - R01 EY025622/EY/NEI NIH HHS/United States
GR  - R01 NS094516/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180320
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Oxepins)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 0 (dibenzo(b,f)oxepin-10-ylmethyl-methyl-prop-2-ynyl-amine)
RN  - 0 (tau Proteins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 2.3.1.48 (p300-CBP-associated factor)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Acetylation/drug effects
MH  - Alzheimer Disease/chemically induced/genetics/*metabolism
MH  - Amyloid beta-Peptides/toxicity
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Motor Activity/drug effects
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type I/*deficiency/genetics
MH  - Oxepins/pharmacology
MH  - Peptide Fragments/toxicity
MH  - Sirtuin 1/*metabolism
MH  - p300-CBP Transcription Factors/*metabolism
MH  - tau Proteins/*metabolism
PMC - PMC6371980
MID - NIHMS1005834
EDAT- 2018/03/22 06:00
MHDA- 2019/09/17 06:00
PMCR- 2019/02/12
CRDT- 2018/03/22 06:00
PHST- 2018/03/22 06:00 [entrez]
PHST- 2018/03/22 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2019/02/12 00:00 [pmc-release]
AID - 11/522/eaao6765 [pii]
AID - 10.1126/scisignal.aao6765 [doi]
PST - epublish
SO  - Sci Signal. 2018 Mar 20;11(522):eaao6765. doi: 10.1126/scisignal.aao6765.