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SIRT1 overexpression ameliorates a mouse model of SOD1-linked amyotrophic lateral sclerosis via HSF1/HSP70i chaperone system

Overview of attention for article published in Molecular Brain, August 2014
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  • Good Attention Score compared to outputs of the same age (71st percentile)

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6 tweeters

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Title
SIRT1 overexpression ameliorates a mouse model of SOD1-linked amyotrophic lateral sclerosis via HSF1/HSP70i chaperone system
Published in
Molecular Brain, August 2014
DOI 10.1186/s13041-014-0062-1
Pubmed ID
Authors

Seiji Watanabe, Natsumi Ageta-Ishihara, Shinji Nagatsu, Keizo Takao, Okiru Komine, Fumito Endo, Tsuyoshi Miyakawa, Hidemi Misawa, Ryosuke Takahashi, Makoto Kinoshita, Koji Yamanaka

Abstract

BackgroundDominant mutations in superoxide dismutase 1 (SOD1) cause degeneration of motor neurons in a subset of inherited amyotrophic lateral sclerosis (ALS). The pathogenetic process mediated by misfolded and/or aggregated mutant SOD1 polypeptides is hypothesized to be suppressed by protein refolding. This genetic study is aimed to test whether mutant SOD1-mediated ALS pathology recapitulated in mice could be alleviated by overexpressing a longevity-related deacetylase SIRT1 whose substrates include a transcription factor heat shock factor 1 (HSF1), the master regulator of the chaperone system.ResultsWe established a line of transgenic mice that chronically overexpress SIRT1 in the brain and spinal cord. While inducible HSP70 (HSP70i) was upregulated in the spinal cord of SIRT1 transgenic mice (PrP-Sirt1), no neurological and behavioral alterations were detected. To test hypothetical benefits of SIRT1 overexpression, we crossbred PrP-Sirt1 mice with two lines of ALS model mice: A high expression line that exhibits a severe phenotype (SOD1G93A-H) or a low expression line with a milder phenotype (SOD1G93A-L). The Sirt1 transgene conferred longer lifespan without altering the time of symptomatic onset in SOD1G93A-L. Biochemical analysis of the spinal cord revealed that SIRT1 induced HSP70i expression through deacetylation of HSF1 and that SOD1G93A-L/PrP-Sirt1 double transgenic mice contained less insoluble SOD1 than SOD1G93A-L mice. Parallel experiments showed that Sirt1 transgene could not rescue a more severe phenotype of SOD1G93A-H transgenic mice partly because their HSP70i level had peaked out.ConclusionsThe genetic supplementation of SIRT1 can ameliorate a mutant SOD1-linked ALS mouse model partly through the activation of the HSF1/HSP70i chaperone system. Future studies shall include testing potential benefits of pharmacological enhancement of the deacetylation activity of SIRT1 after the onset of the symptom.

Twitter Demographics

The data shown below were collected from the profiles of 6 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 85 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Japan 1 1%
Malaysia 1 1%
Unknown 82 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 18 21%
Researcher 14 16%
Student > Bachelor 11 13%
Student > Master 10 12%
Student > Doctoral Student 6 7%
Other 19 22%
Unknown 7 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 19 22%
Neuroscience 16 19%
Biochemistry, Genetics and Molecular Biology 15 18%
Medicine and Dentistry 10 12%
Chemistry 4 5%
Other 11 13%
Unknown 10 12%

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 12 September 2014.
All research outputs
#6,351,871
of 21,326,395 outputs
Outputs from Molecular Brain
#303
of 1,053 outputs
Outputs of similar age
#60,939
of 215,416 outputs
Outputs of similar age from Molecular Brain
#1
of 1 outputs
Altmetric has tracked 21,326,395 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 1,053 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has gotten more attention than average, scoring higher than 71% 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 215,416 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 71% 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