↓ Skip to main content

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
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#9 of 1,151)
  • High Attention Score compared to outputs of the same age (97th percentile)

Mentioned by

news
10 news outlets
blogs
3 blogs
twitter
44 tweeters
facebook
8 Facebook pages
reddit
1 Redditor
video
1 video uploader

Citations

dimensions_citation
27 Dimensions

Readers on

mendeley
75 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
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.

Twitter Demographics

The data shown below were collected from the profiles of 44 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 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 75 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 16 21%
Researcher 15 20%
Student > Master 11 15%
Student > Ph. D. Student 10 13%
Student > Postgraduate 4 5%
Other 10 13%
Unknown 9 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 25%
Neuroscience 13 17%
Medicine and Dentistry 13 17%
Agricultural and Biological Sciences 10 13%
Psychology 4 5%
Other 6 8%
Unknown 10 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 121. 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 19 August 2021.
All research outputs
#219,962
of 19,002,645 outputs
Outputs from Acta Neuropathologica Communications
#9
of 1,151 outputs
Outputs of similar age
#6,627
of 288,982 outputs
Outputs of similar age from Acta Neuropathologica Communications
#1
of 1 outputs
Altmetric has tracked 19,002,645 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 1,151 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.8. This one has done particularly well, scoring higher than 99% 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 288,982 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 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