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O-GlcNAc regulation of autophagy and α-synuclein homeostasis; implications for Parkinson’s disease

Overview of attention for article published in Molecular Brain, July 2017
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  • Above-average Attention Score compared to outputs of the same age (62nd percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

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8 X users

Citations

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69 Dimensions

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93 Mendeley
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1 CiteULike
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Title
O-GlcNAc regulation of autophagy and α-synuclein homeostasis; implications for Parkinson’s disease
Published in
Molecular Brain, July 2017
DOI 10.1186/s13041-017-0311-1
Pubmed ID
Authors

Willayat Y. Wani, Xiaosen Ouyang, Gloria A. Benavides, Matthew Redmann, Stacey S. Cofield, John J. Shacka, John C. Chatham, Victor Darley-Usmar, Jianhua Zhang

Abstract

Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels. To determine whether increased O-GlcNAcylation affects neuronal function and survival, we exposed rat primary cortical neurons to thiamet G, a highly selective inhibitor of the enzyme which removes the O-GlcNAc modification from target proteins, O-GlcNAcase (OGA). We found that inhibition of OGA by thiamet G at nanomolar concentrations significantly increased protein O-GlcNAcylation, activated MTOR, decreased autophagic flux, and increased α-synuclein accumulation, while sparing proteasomal activities. Inhibition of MTOR by rapamycin decreased basal levels of protein O-GlcNAcylation, decreased AKT activation and partially reversed the effect of thiamet G on α-synuclein monomer accumulation. Taken together we have provided evidence that excessive O-GlcNAcylation is detrimental to neurons by inhibition of autophagy and by increasing α-synuclein accumulation.

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X Demographics

The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 93 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 17 18%
Student > Ph. D. Student 15 16%
Student > Master 11 12%
Student > Bachelor 9 10%
Other 6 6%
Other 12 13%
Unknown 23 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 20%
Neuroscience 16 17%
Agricultural and Biological Sciences 9 10%
Pharmacology, Toxicology and Pharmaceutical Science 6 6%
Chemistry 6 6%
Other 11 12%
Unknown 26 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 April 2018.
All research outputs
#7,287,407
of 22,990,068 outputs
Outputs from Molecular Brain
#356
of 1,117 outputs
Outputs of similar age
#115,946
of 315,216 outputs
Outputs of similar age from Molecular Brain
#9
of 23 outputs
Altmetric has tracked 22,990,068 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 1,117 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has gotten more attention than average, scoring higher than 67% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 315,216 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.