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Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture

Overview of attention for article published in Molecular Neurodegeneration, May 2017
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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 (82nd percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

Mentioned by

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1 news outlet
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2 tweeters

Citations

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33 Dimensions

Readers on

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57 Mendeley
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Title
Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture
Published in
Molecular Neurodegeneration, May 2017
DOI 10.1186/s13024-017-0176-x
Pubmed ID
Authors

Takashi Miyamoto, Liana Stein, Reuben Thomas, Biljana Djukic, Praveen Taneja, Joseph Knox, Keith Vossel, Lennart Mucke

Abstract

Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer's disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear. We established a cell-based assay to quantify excitotoxicity in primary cultures of mouse hippocampal neurons and investigated the role of tau in exicitotoxicity by modulating neuronal tau expression through genetic ablation or transduction with lentiviral vectors expressing anti-tau shRNA or constructs encoding wildtype versus mutant mouse tau. We demonstrate that shRNA-mediated knockdown of tau reduces glutamate-induced, NMDA receptor-dependent Ca(2+) influx and neurotoxicity in neurons from wildtype mice. Conversely, expression of wildtype mouse tau enhances Ca(2+) influx and excitotoxicity in tau-deficient (Mapt (-/-)) neurons. Reconstituting tau expression in Mapt (-/-) neurons with mutant forms of tau reveals that the tau-related enhancement of Ca(2+) influx and excitotoxicity depend on the phosphorylation of tau at tyrosine 18 (pY18), which is mediated by the tyrosine kinase Fyn. These effects are most evident at pathologically elevated concentrations of glutamate, do not involve GluN2B-containing NMDA receptors, and do not require binding of Fyn to tau's major interacting PxxP motif or of tau to microtubules. Although tau has been implicated in diverse neurological diseases, its most pathogenic forms remain to be defined. Our study suggests that reducing the formation or level of pY18-tau can counteract excitotoxicity by diminishing NMDA receptor-dependent Ca(2+) influx.

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

Geographical breakdown

Country Count As %
Unknown 57 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 33%
Student > Master 7 12%
Researcher 6 11%
Student > Doctoral Student 5 9%
Student > Bachelor 4 7%
Other 9 16%
Unknown 7 12%
Readers by discipline Count As %
Neuroscience 22 39%
Biochemistry, Genetics and Molecular Biology 9 16%
Agricultural and Biological Sciences 8 14%
Pharmacology, Toxicology and Pharmaceutical Science 4 7%
Chemistry 2 4%
Other 3 5%
Unknown 9 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 06 April 2018.
All research outputs
#1,368,339
of 12,768,104 outputs
Outputs from Molecular Neurodegeneration
#150
of 551 outputs
Outputs of similar age
#45,124
of 263,424 outputs
Outputs of similar age from Molecular Neurodegeneration
#10
of 22 outputs
Altmetric has tracked 12,768,104 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 551 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.1. This one has gotten more attention than average, scoring higher than 70% 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 263,424 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 22 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.