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Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior ♦

Overview of attention for article published in Journal of Biological Chemistry, March 2014
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (79th percentile)
  • High Attention Score compared to outputs of the same age and source (81st percentile)

Mentioned by

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2 X users
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2 patents
wikipedia
1 Wikipedia page

Citations

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60 Dimensions

Readers on

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100 Mendeley
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Title
Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior ♦
Published in
Journal of Biological Chemistry, March 2014
DOI 10.1074/jbc.m113.542654
Pubmed ID
Authors

Christine E Gee, Daniel Peterlik, Christoph Neuhäuser, Rochdi Bouhelal, Klemens Kaupmann, Grit Laue, Nicole Uschold-Schmidt, Dominik Feuerbach, Kaspar Zimmermann, Silvio Ofner, John F Cryan, Herman van der Putten, Markus Fendt, Ivo Vranesic, Ralf Glatthar, Peter J Flor

Abstract

The metabotropic glutamate receptor subtype 7 (mGlu7) is an important presynaptic regulator of neurotransmission in the mammalian CNS. mGlu7 function has been linked to autism, drug abuse, anxiety, and depression. Despite this, it has been difficult to develop specific blockers of native mGlu7 signaling in relevant brain areas such as amygdala and limbic cortex. Here, we present the mGlu7-selective antagonist 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one (XAP044), which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm. There was no effect of XAP044 on LTP of mGlu7-deficient mice, indicating that this pharmacological effect is mGlu7-dependent. Unexpectedly and in contrast to all previous mGlu7-selective drugs, XAP044 does not act via the seven-transmembrane region but rather via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region generally known for orthosteric agonist binding. This was shown by chimeric receptor studies in recombinant cell line assays. XAP044 demonstrates good brain exposure and wide spectrum anti-stress and antidepressant- and anxiolytic-like efficacy in rodent behavioral paradigms. XAP044 reduces freezing during acquisition of Pavlovian fear and reduces innate anxiety, which is consistent with the phenotypes of mGlu7-deficient mice, the results of mGlu7 siRNA knockdown studies, and the inhibition of amygdala LTP by XAP044. Thus, we present an mGlu7 antagonist with a novel molecular mode of pharmacological action, providing significant application potential in psychiatry. Modeling the selective interaction between XAP044 and mGlu7's Venus flytrap domain, whose three-dimensional structure is already known, will facilitate future drug development supported by computer-assisted drug design.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 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 100 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Germany 1 1%
Ireland 1 1%
Unknown 97 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 23%
Student > Bachelor 14 14%
Researcher 13 13%
Student > Master 13 13%
Student > Doctoral Student 4 4%
Other 11 11%
Unknown 22 22%
Readers by discipline Count As %
Neuroscience 18 18%
Agricultural and Biological Sciences 13 13%
Biochemistry, Genetics and Molecular Biology 10 10%
Chemistry 10 10%
Psychology 8 8%
Other 16 16%
Unknown 25 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 July 2022.
All research outputs
#4,835,465
of 25,373,627 outputs
Outputs from Journal of Biological Chemistry
#12,344
of 85,238 outputs
Outputs of similar age
#44,938
of 236,028 outputs
Outputs of similar age from Journal of Biological Chemistry
#76
of 453 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 85,238 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has done well, scoring higher than 84% 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 236,028 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 79% of its contemporaries.
We're also able to compare this research output to 453 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.