Evidence map›Paper›PMID 14672996›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003

Selective activation induced cleavage of the NR2B subunit by calpain.

Kelly L Simpkins, Rodney P Guttmann, Yina Dong, Zhaoming Chen, Set Sokol, Robert W Neumar, David R Lynch

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 150 citations in OpenAlex.

  1. Article
  2. Decoding the mechanisms of amyloid-β in synaptic toxicity.Journal of Alzheimer's disease : JAD · 2026
    Review
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  7. Article
  8. Article
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  13. NMDA Receptor and Its Emerging Role in Cancer.International journal of molecular sciences · 2023
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Kelly L SimpkinsDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-4306, USA.
Rodney P Guttmann
Yina Dong
Zhaoming Chen
Set Sokol
Robert W Neumar
David R Lynch
Children's Hospital of Philadelphia · USUniversity of Kentucky · USUniversity of Pennsylvania · US

Funding

Regulation of NMDA Receptors in Excitotoxicity by Calpain and FYNR01NS045986 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI LYNCH, DAVID ROBINSON · 2003 to 2011
$2.9M
NMDA RECEPTORS, PROTEIN KINASE C, AND EXCITOTOXICITYR01NS039126 · NINDS · CHILDREN'S HOSPITAL OF PHILADELPHIA · PI LYNCH, DAVID ROBINSON · 1999 to 2002
$723k
Regulation of NMDA Receptors in Excitotoxicity by Calpain and FYNR56NS045986 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI LYNCH, DAVID ROBINSON · 2007 to 2007
$413k
NINDS NIH HHS NS39126NINDS NIH HHS NS45986NINDS NIH HHS R01 NS045986NINDS NIH HHS R56 NS045986
6 · The paper itself

Abstract

Although activation of calcium-activated neutral protease (calpain) by the NMDA receptor has been suggested to play critical roles in synaptic modulation and neurologic disease, the nature of its substrates has not been completely defined. In this study, we examined the ability of calpain to cleave the NMDA receptor in cultured hippocampal neurons. Activation of the NMDA receptor by agonist application led to rapid calpain-specific proteolysis of spectrin and decreased levels of NR2A/2B subunits. Cleavage of the NR2A/2B subunit created a 115 kDa product that retained the ability to bind 125I-MK-801 and is predicted to be active. Increases in levels of this product appeared within 5 min of NMDA receptor activation and were stable for periods of >30 min. Subtype-specific antibodies demonstrated that the NR2B subunit was cleaved in these primary cultures, but the NR2A subunit was not. An inhibitor of calpain blocked both the decrease of intact NR2B and the increase of the low molecular weight form, whereas neither caspase nor cathepsin inhibitors had an effect on these events. Cell surface biotinylation experiments demonstrated that the 115 kDa fragment remained on the cell surface. This NR2B fragment was also found in the rat hippocampus after transient forebrain ischemia, showing that this process also occurs in vivo. This suggests that calpain-mediated cleavage of the NR2B subunit occurs in neurons and gives rise to active NMDA receptor forms present on the cell surface after excitotoxic glutamatergic stimulation. Such forms could contribute to excitotoxicity and synaptic remodeling.

Indexed as

AnimalsBrain IschemiaCalpainCell LineCells, CulturedEnzyme ActivationGlutamic AcidHippocampusHumansMaleNeuronsProtein SubunitsRatsRats, Long-EvansReceptors, N-Methyl-D-AspartateCalpainGlutamic AcidNR2B NMDA receptorProtein SubunitsReceptors, N-Methyl-D-Aspartate

Identifiers

PMID14672996
PMCPMC6740527
OpenAlexW1680575362

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.