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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Positive Modulatory Interactions of NMDA Receptor GluN1/2B Ligand Binding Domains Attenuate Antagonists Activity
|
|---|---|
| Published in |
Frontiers in Pharmacology, May 2017
|
| DOI | 10.3389/fphar.2017.00229 |
| Pubmed ID | |
| Authors |
Douglas Bledsoe, Ceyhun Tamer, Ivana Mesic, Christian Madry, Bradley G. Klein, Bodo Laube, Blaise M. Costa |
| Abstract |
N-methyl D-aspartate receptors (NMDAR) play crucial role in normal brain function and pathogenesis of neurodegenerative and psychiatric disorders. Functional tetra-heteromeric NMDAR contains two obligatory GluN1 subunits and two identical or different non-GluN1 subunits that include six different gene products; four GluN2 (A-D) and two GluN3 (A-B) subunits. The heterogeneity of subunit combination facilities the distinct function of NMDARs. All GluN subunits contain an extracellular N-terminal Domain (NTD) and ligand binding domain (LBD), transmembrane domain (TMD) and an intracellular C-terminal domain (CTD). Interaction between the GluN1 and co-assembling GluN2/3 subunits through the LBD has been proven crucial for defining receptor deactivation mechanisms that are unique for each combination of NMDAR. Modulating the LBD interactions has great therapeutic potential. In the present work, by amino acid point mutations and electrophysiology techniques, we have studied the role of LBD interactions in determining the effect of well-characterized pharmacological agents including agonists, competitive antagonists, and allosteric modulators. The results reveal that agonists (glycine and glutamate) potency was altered based on mutant amino acid sidechain chemistry and/or mutation site. Most antagonists inhibited mutant receptors with higher potency; interestingly, clinically used NMDAR channel blocker memantine was about three-fold more potent on mutated receptors (N521A, N521D, and K531A) than wild type receptors. These results provide novel insights on the clinical pharmacology of memantine, which is used for the treatment of mild to moderate Alzheimer's disease. In addition, these findings demonstrate the central role of LBD interactions that can be exploited to develop novel NMDAR based therapeutics. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 50% |
| Switzerland | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 23 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 26% |
| Student > Bachelor | 5 | 22% |
| Researcher | 4 | 17% |
| Student > Master | 3 | 13% |
| Other | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 3 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 26% |
| Neuroscience | 5 | 22% |
| Biochemistry, Genetics and Molecular Biology | 3 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 9% |
| Medicine and Dentistry | 2 | 9% |
| Other | 2 | 9% |
| Unknown | 3 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 05 December 2017.
All research outputs
#14,935,459
of 22,971,207 outputs
Outputs from Frontiers in Pharmacology
#5,258
of 16,248 outputs
Outputs of similar age
#184,978
of 310,718 outputs
Outputs of similar age from Frontiers in Pharmacology
#83
of 237 outputs
Altmetric has tracked 22,971,207 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,248 research outputs from this source. They receive a mean Attention Score of 5.0. This one has gotten more attention than average, scoring higher than 60% 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 310,718 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 237 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 57% of its contemporaries.