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Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease

Overview of attention for article published in Acta Neuropathologica Communications, March 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#22 of 1,593)
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (95th percentile)

Mentioned by

news
10 news outlets
blogs
3 blogs
twitter
41 X users
facebook
8 Facebook pages
reddit
1 Redditor
video
2 YouTube creators

Citations

dimensions_citation
49 Dimensions

Readers on

mendeley
100 Mendeley
Title
Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease
Published in
Acta Neuropathologica Communications, March 2018
DOI 10.1186/s40478-018-0518-0
Pubmed ID
Authors

Dagmar E. Ehrnhoefer, Dale D. O. Martin, Mandi E. Schmidt, Xiaofan Qiu, Safia Ladha, Nicholas S. Caron, Niels H. Skotte, Yen T. N. Nguyen, Kuljeet Vaid, Amber L. Southwell, Sabine Engemann, Sonia Franciosi, Michael R. Hayden

Abstract

Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

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X Demographics

The data shown below were collected from the profiles of 41 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 100 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 100 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 17 17%
Researcher 16 16%
Student > Ph. D. Student 13 13%
Student > Master 11 11%
Other 5 5%
Other 13 13%
Unknown 25 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 18 18%
Medicine and Dentistry 16 16%
Neuroscience 16 16%
Agricultural and Biological Sciences 10 10%
Psychology 5 5%
Other 9 9%
Unknown 26 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 112. 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 27 February 2023.
All research outputs
#380,559
of 25,712,965 outputs
Outputs from Acta Neuropathologica Communications
#22
of 1,593 outputs
Outputs of similar age
#8,672
of 348,355 outputs
Outputs of similar age from Acta Neuropathologica Communications
#1
of 24 outputs
Altmetric has tracked 25,712,965 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,593 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.5. This one has done particularly well, scoring higher than 98% 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 348,355 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.