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Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer’s disease mouse models

Overview of attention for article published in Molecular Brain, April 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#40 of 637)
  • High Attention Score compared to outputs of the same age (83rd percentile)

Mentioned by

news
1 news outlet
twitter
7 tweeters

Citations

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10 Dimensions

Readers on

mendeley
29 Mendeley
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Title
Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer’s disease mouse models
Published in
Molecular Brain, April 2018
DOI 10.1186/s13041-018-0364-9
Pubmed ID
Authors

Khaled S. Abd-Elrahman, Alison Hamilton, Maryam Vasefi, Stephen S. G. Ferguson

Abstract

Alzheimer's disease (AD) is characterized by neurotoxicity mediated by the accumulation of beta amyloid (Aβ) oligomers, causing neuronal loss and progressive cognitive decline. Genetic deletion or chronic pharmacological inhibition of mGluR5 by the negative allosteric modulator CTEP, rescues cognitive function and reduces Aβ aggregation in both APPswe/PS1ΔE9 and 3xTg-AD mouse models of AD. In late onset neurodegenerative diseases, such as AD, defects arise at different stages of the autophagy pathway. Here, we show that mGluR5 cell surface expression is elevated in APPswe/PS1ΔE9 and 3xTg-AD mice. This is accompanied by reduced autophagy (accumulation of p62) as the consequence of increased ZBTB16 expression and reduced ULK1 activity, as we have previously observed in Huntington's disease (HD). The chronic (12 week) inhibition of mGluR5 with CTEP in APPswe/PS1ΔE9 and 3xTg-AD mice prevents the observed increase in mGluR5 surface expression. In addition, mGluR5 inactivation facilitates the loss of ZBTB16 expression and ULK1 activation as a consequence of ULK-Ser757 dephosphorylation, which promotes the loss of expression of the autophagy marker p62. Moreover, the genetic ablation of mGluR5 in APPswe/PS1ΔE9 mice activated autophagy via similar mechanisms to pharmacological blockade. This study provides further evidence that mGluR5 overactivation contributes to inhibition of autophagy and can result in impaired clearance of neurotoxic aggregates in multiple neurodegenerative diseases. Thus, it provides additional support for the potential of mGluR5 inhibition as a general therapeutic strategy for neurodegenerative diseases such as AD and HD.

Twitter Demographics

The data shown below were collected from the profiles of 7 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 17%
Student > Master 5 17%
Student > Bachelor 4 14%
Other 2 7%
Student > Postgraduate 2 7%
Other 5 17%
Unknown 6 21%
Readers by discipline Count As %
Neuroscience 8 28%
Biochemistry, Genetics and Molecular Biology 4 14%
Pharmacology, Toxicology and Pharmaceutical Science 3 10%
Medicine and Dentistry 3 10%
Agricultural and Biological Sciences 2 7%
Other 3 10%
Unknown 6 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 23 October 2018.
All research outputs
#1,310,671
of 13,793,900 outputs
Outputs from Molecular Brain
#40
of 637 outputs
Outputs of similar age
#44,749
of 274,404 outputs
Outputs of similar age from Molecular Brain
#1
of 1 outputs
Altmetric has tracked 13,793,900 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 637 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done particularly well, scoring higher than 93% 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 274,404 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them