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Effect of rapamycin on lysosomal accumulation in a CRISPR/Cas9‐based cellular model of VPS13A deficiency

Overview of attention for article published in Journal of Cellular and Molecular Medicine, May 2023
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • High Attention Score compared to outputs of the same age and source (91st percentile)

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Title
Effect of rapamycin on lysosomal accumulation in a CRISPR/Cas9‐based cellular model of VPS13A deficiency
Published in
Journal of Cellular and Molecular Medicine, May 2023
DOI 10.1111/jcmm.17768
Pubmed ID
Authors

A. R. Tornero‐Écija, M. A. Navas, S. Muñoz‐Braceras, O. Vincent, R. Escalante

Abstract

VPS13A is a lipid transfer protein localized at different membrane contact sites between organelles, and mutations in the corresponding gene produce a rare neurodegenerative disease called chorea-acanthocytosis (ChAc). Previous studies showed that VPS13A depletion in HeLa cells results in an accumulation of endosomal and lysosomal markers, suggesting a defect in lysosomal degradation capacity leading to partial autophagic dysfunction. Our goal was to determine whether compounds that modulate the endo-lysosomal pathway could be beneficial in the treatment of ChAc. To test this hypothesis, we first generated a KO model using CRISPR/Cas9 to study the consequences of the absence of VPS13A in HeLa cells. We found that inactivation of VPS13A impairs cell growth, which precludes the use of isolated clones due to the undesirable selection of edited clones with residual protein expression. Therefore, we optimized the use of pool cells obtained shortly after transfection with CRISPR/Cas9 components. These cells are a mixture of wild-type and edited cells that allow a comparative analysis of phenotypes and avoids the selection of clones with residual level of VPS13A expression after long-term growth. Consistent with previous observations by siRNA inactivation, VPS13A inactivation by CRISPR/Cas9 resulted in accumulation of the endo-lysosomal markers RAB7A and LAMP1. Notably, we observed that rapamycin partially suppressed the difference in lysosome accumulation between VPS13A KO and WT cells, suggesting that modulation of the autophagic and lysosomal pathway could be a therapeutic target in the treatment of ChAc.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 1 20%
Student > Ph. D. Student 1 20%
Student > Master 1 20%
Unknown 2 40%
Readers by discipline Count As %
Unspecified 1 20%
Biochemistry, Genetics and Molecular Biology 1 20%
Neuroscience 1 20%
Unknown 2 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 9. 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 01 June 2023.
All research outputs
#3,892,084
of 24,356,663 outputs
Outputs from Journal of Cellular and Molecular Medicine
#363
of 3,611 outputs
Outputs of similar age
#66,189
of 380,336 outputs
Outputs of similar age from Journal of Cellular and Molecular Medicine
#4
of 34 outputs
Altmetric has tracked 24,356,663 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,611 research outputs from this source. They receive a mean Attention Score of 3.9. This one has done well, scoring higher than 89% 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 380,336 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 82% of its contemporaries.
We're also able to compare this research output to 34 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 91% of its contemporaries.