Evidence map›Paper›PMID 26441823›Full record

ArticleFrontiers in neurology2015

Protein Citrullination: A Proposed Mechanism for Pathology in Traumatic Brain Injury.

Rachel C Lazarus, John E Buonora, Michael N Flora, James G Freedy, Gay R Holstein, Giorgio P Martinelli, David M Jacobowitz, Gregory P Mueller

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

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  13. Compartmentalized citrullination in Muller glial endfeet during retinal degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2022
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  17. Putative Roles for Peptidylarginine Deiminases in COVID-19.International journal of molecular sciences · 2020
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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

8 authors at 3 institutions in 1 country.

Rachel C LazarusProgram in Neuroscience, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
John E BuonoraUS Army Graduate Program in Anesthesia Nursing , Fort Sam Houston, TX , USA.
Michael N FloraDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
James G FreedyDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
Gay R HolsteinDepartment of Neurology, Icahn School of Medicine at Mount Sinai , New York, NY , USA.
Giorgio P MartinelliDepartment of Neurology, Icahn School of Medicine at Mount Sinai , New York, NY , USA.
David M JacobowitzProgram in Neuroscience, Uniformed Services University of the Health Sciences , Bethesda, MD , USA ; Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
Gregory P MuellerProgram in Neuroscience, Uniformed Services University of the Health Sciences , Bethesda, MD , USA ; Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA ; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
Uniformed Services University of the Health Sciences · USIcahn School of Medicine at Mount Sinai · USUnited States Department of the Army · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protein citrullination is a calcium-driven post-translational modification proposed to play a causative role in the neurodegenerative disorders of Alzheimer's disease, multiple sclerosis (MS), and prion disease. Citrullination can result in the formation of antigenic epitopes that underlie pathogenic autoimmune responses. This phenomenon, which is best understood in rheumatoid arthritis, may play a role in the chronic dysfunction following traumatic brain injury (TBI). Despite substantial evidence of aberrations in calcium signaling following TBI, there is little understanding of how TBI alters citrullination in the brain. The present investigation addressed this gap by examining the effects of TBI on the distribution of protein citrullination and on the specific cell types involved. Immunofluorescence revealed that controlled cortical impact in rats profoundly up--regulated protein citrullination in the cerebral cortex, external capsule, and hippocampus. This response was exclusively seen in astrocytes; no such effects were observed on the status of protein citrullination in neurons, oligodendrocytes or microglia. Further, proteomic analyses demonstrated that the effects of TBI on citrullination were confined to a relatively small subset of neural proteins. Proteins most notably affected were those also reported to be citrullinated in other disorders, including prion disease and MS. In vivo findings were extended in an in vitro model of simulated TBI employing normal human astrocytes. Pharmacologically induced calcium excitotoxicity was shown to activate the citrullination and breakdown of glial fibrillary acidic protein, producing a novel candidate TBI biomarker and potential target for autoimmune recognition. In summary, these findings demonstrate that the effects of TBI on protein citrullination are selective with respect to brain region, cell type, and proteins modified, and may contribute to a role for autoimmune dysfunction in chronic pathology following TBI.

Indexed as

astrocytescalciumcitrullinationglial fibrillary acidic proteintraumatic brain injury

Identifiers

PMID26441823
PMCPMC4585288
OpenAlexW1884970356

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Registered trials

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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.