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Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis

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

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • High Attention Score compared to outputs of the same age and source (86th percentile)

Mentioned by

news
1 news outlet
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8 X users
patent
1 patent

Citations

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80 Dimensions

Readers on

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96 Mendeley
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Title
Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis
Published in
Acta Neuropathologica Communications, August 2018
DOI 10.1186/s40478-018-0586-1
Pubmed ID
Authors

L. McGurk, J. Mojsilovic-Petrovic, V. M. Van Deerlin, J. Shorter, R. G. Kalb, V. M. Lee, J. Q. Trojanowski, E. B. Lee, N. M. Bonini

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2-5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis.

X Demographics

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 96 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 96 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 21%
Researcher 14 15%
Student > Master 10 10%
Student > Bachelor 9 9%
Student > Doctoral Student 6 6%
Other 15 16%
Unknown 22 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 25 26%
Neuroscience 10 10%
Agricultural and Biological Sciences 9 9%
Medicine and Dentistry 7 7%
Chemistry 6 6%
Other 10 10%
Unknown 29 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 17. 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 28 May 2020.
All research outputs
#1,865,000
of 23,102,082 outputs
Outputs from Acta Neuropathologica Communications
#248
of 1,398 outputs
Outputs of similar age
#41,096
of 335,210 outputs
Outputs of similar age from Acta Neuropathologica Communications
#5
of 36 outputs
Altmetric has tracked 23,102,082 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,398 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one has done well, scoring higher than 82% 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 335,210 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 87% of its contemporaries.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.