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Targeting TDP-43 phosphorylation by Casein Kinase-1δ inhibitors: a novel strategy for the treatment of frontotemporal dementia

Overview of attention for article published in Molecular Neurodegeneration, April 2016
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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 (86th percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

Mentioned by

news
1 news outlet
twitter
2 tweeters
wikipedia
1 Wikipedia page

Citations

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18 Dimensions

Readers on

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41 Mendeley
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Title
Targeting TDP-43 phosphorylation by Casein Kinase-1δ inhibitors: a novel strategy for the treatment of frontotemporal dementia
Published in
Molecular Neurodegeneration, April 2016
DOI 10.1186/s13024-016-0102-7
Pubmed ID
Authors

Carolina Alquezar, Irene G. Salado, Ana de la Encarnación, Daniel I. Pérez, Fermín Moreno, Carmen Gil, Adolfo López de Munain, Ana Martínez, Ángeles Martín-Requero

Abstract

Mutations in the progranulin gene (GRN) are the most common cause of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). TDP-43 pathology is characterized by the hyperphosphorylation of the protein at Serine 409/410 residues. Casein kinase-1δ (CK-1δ) was reported to phosphorylate TDP-43 directly. Previous works from our laboratory described the presence of CDK6/pRb-dependent cell cycle alterations, and cytosolic accumulation of TDP-43 protein in lymphoblast from FTLD-TDP patients carriers of a loss-of function mutation in GRN gene (c.709-1G > A). In this work, we have investigated the effects of two brain penetrant CK-1δ inhibitors (IGS-2.7 and IGS-3.27) designed and synthetized in our laboratory on cell proliferation, TDP-43 phosphorylation and subcellular localization, as well as their effects on the known nuclear TDP-43 function repressing the expression of CDK6. We report here that both CK-1δ inhibitors (IGS-2.7 and IGS-3.27) normalized the proliferative activity of PGRN-deficient lymphoblasts by preventing the phosphorylation of TDP-43 fragments, its nucleo-cytosol translocation and the overactivation of the CDK6/pRb cascade. Moreover, ours results show neuroprotective effects of CK-1δ inhibitors in a neuronal cell model of induced TDP-43 phosphorylation. Our results suggest that modulating CK-1δ activity could be considered a novel therapeutic approach for the treatment of FTLD-TDP and other TDP-43 proteinopathies.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 27%
Researcher 7 17%
Student > Master 5 12%
Student > Bachelor 5 12%
Student > Postgraduate 2 5%
Other 5 12%
Unknown 6 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 29%
Neuroscience 9 22%
Agricultural and Biological Sciences 6 15%
Pharmacology, Toxicology and Pharmaceutical Science 3 7%
Social Sciences 2 5%
Other 2 5%
Unknown 7 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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 26 April 2019.
All research outputs
#1,398,373
of 14,723,618 outputs
Outputs from Molecular Neurodegeneration
#114
of 614 outputs
Outputs of similar age
#33,887
of 261,133 outputs
Outputs of similar age from Molecular Neurodegeneration
#2
of 8 outputs
Altmetric has tracked 14,723,618 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 614 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one has done well, scoring higher than 80% 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 261,133 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 86% of its contemporaries.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 6 of them.