Evidence map›Paper›PMID 36036549›Full record

ArticleJournal of cellular physiology2024

Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease.

Garrett A Clemons, Alexandre Couto E Silva, Christina H Acosta, Mariana Sayuri Berto Udo, Vesna Tesic, Krista M Rodgers, Celeste Yin-Chieh Wu, Cristiane T Citadin, Reggie Hui-Chao Lee, Jake T Neumann and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cellular physiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

17 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Blockade of AGeroScience · 2025
    Article
  7. Review
  8. Review
  9. PRMT3 and CARM1: Emerging Epigenetic Targets in Cancer.Journal of cellular and molecular medicine · 2025
    Review
  10. Review
  11. Review
  12. The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Amino acid metabolism in health and disease.Signal transduction and targeted therapy · 2023
    Review
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

14 authors at 4 institutions in 1 country.

Garrett A ClemonsDepartment of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Alexandre Couto E SilvaOregon Health and Science University, Portland, Oregon, USA.
Christina H AcostaDepartment of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Mariana Sayuri Berto UdoDepartment of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Vesna TesicDepartment of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Krista M RodgersDepartment of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Celeste Yin-Chieh WuDepartment of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Cristiane T CitadinDepartment of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Reggie Hui-Chao LeeDepartment of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Jake T NeumannDepartment of Biomedical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, West Virginia, USA.
Shailaja AllaniCenter for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, Florida, USA.ORCID 0000-0002-1900-2933
Howard PrenticeDepartment of Biomedical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, USA.
Quanguang ZhangDepartment of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Hung Wen LinDepartment of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.ORCID 0000-0003-1010-5423
Louisiana State University Health Sciences Center Shreveport · USFlorida Atlantic University · USOregon Health & Science University · USWest Virginia School of Osteopathic Medicine · US

Funding

Vascular Regulatory Mechanisms of Palmitic Acid Methyl EsterR01NS096225 · NINDS · LOUISIANA STATE UNIV HSC SHREVEPORT · PI LIN, HUNG WEN (KEVIN) · 2017 to 2021
$1.6M
Kinase regulation in cerebral ischemiaR01NS126273 · NINDS · UNIVERSITY OF SOUTH FLORIDA · PI LEE, REGGIE HUI-CHAO · 2022 to 2025
$1.5M
American Heart Association-American Stroke Association 19TPA34850047NINDS NIH HHS R01 NS096225NINDS NIH HHS R01 NS126273
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the leading cause of mortality, disability, and long-term care burden in the United States, with women comprising the majority of AD diagnoses. While AD-related dementia is associated with tau and amyloid beta accumulation, concurrent derangements in cerebral blood flow have been observed alongside these proteinopathies in humans and rodent models. The homeostatic production of nitric oxide synthases (NOS) becomes uncoupled in AD which leads to decreased NO-mediated vasodilation and oxidative stress via the production of peroxynitrite (ONOO-∙) superoxide species. Here, we investigate the role of the novel protein arginine methyltransferase 4 (PRMT4) enzyme function and its downstream product asymmetric dimethyl arginine (ADMA) as it relates to NOS dysregulation and cerebral blood flow in AD. ADMA (type-1 PRMT product) has been shown to bind NOS as a noncanonic ligand causing enzymatic dysfunction. Our results from RT-qPCR and protein analyses suggest that aged (9-12 months) female mice bearing tau- and amyloid beta-producing transgenic mutations (3xTg-AD) express higher levels of PRMT4 in the hippocampus when compared to age- and sex-matched C57BL6/J mice. In addition, we performed studies to quantify the expression and activity of different NOS isoforms. Furthermore, laser speckle contrast imaging analysis was indicative that 3xTg-AD mice have dysfunctional NOS activity, resulting in reduced production of NO metabolites, enhanced production of free-radical ONOO-, and decreased cerebral blood flow. Notably, the aforementioned phenomena can be reversed via pharmacologic PRMT4 inhibition. Together, these findings implicate the potential importance of PRMT4 signaling in the pathogenesis of Alzheimer's-related cerebrovascular derangement.

Indexed as

Alzheimer DiseaseArginineCerebrovascular CirculationMice, TransgenicProtein-Arginine N-MethyltransferasesAgingAmyloid beta-PeptidesAnimalsDisease Models, AnimalFemaleMaleMiceMice, Inbred C57BLNitric OxideNitric Oxide SynthaseOxidative StressAmyloid beta-PeptidesArgininecoactivator-associated arginine methyltransferase 1Nitric OxideNitric Oxide SynthaseN,N-dimethylarginineProtein-Arginine N-Methyltransferasestau ProteinsAlzheimer's diseasecerebral blood flownitric oxide synthase uncouplingprotein arginine methyltransferase

Identifiers

PMID36036549
PMCPMC9971360
OpenAlexW4293476250

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.