Evidence map›Paper›PMID 27180285›Full record

ArticleNeuroscience2016

Simvastatin inhibits protein isoprenylation in the brain.

Stephen M Ostrowski, Kachael Johnson, Matthew Siefert, Sam Shank, Luigi Sironi, Benjamin Wolozin, Gary E Landreth, Assem G Ziady

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

Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
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  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Applying causal models to explore the mechanism of action of simvastatin in progressive multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  12. Novel Approaches for the Treatment of Alzheimer's and Parkinson's Disease.International journal of molecular sciences · 2019
    Review
  13. Review
  14. 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

8 authors at 5 institutions in 2 countries.

Stephen M OstrowskiDepartment of Neurosciences, Case Western Reserve University, Cleveland, OH, USA.
Kachael JohnsonDepartment of Pediatrics, Emory University, Atlanta, GA, USA; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Matthew SiefertDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Sam ShankDepartment of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
Luigi SironiDepartment of Pharmacological and Biomolecular Sciences, University of Milan, and Centro Cardiologico Monzino, Milan, Italy.
Benjamin WolozinDepartments of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA, USA.
Gary E LandrethDepartment of Neurosciences, Case Western Reserve University, Cleveland, OH, USA.
Assem G ZiadyDepartment of Pediatrics, Emory University, Atlanta, GA, USA; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA. Electronic address: assem.ziady@cchmc.org.
Case Western Reserve University · USCincinnati Children's Hospital Medical Center · USBoston University · USCentro Cardiologico Monzino · ITEmory University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Dysregulation of Nrf2 in CF epitheliaR01HL109362 · NHLBI · EMORY UNIVERSITY · PI ZIADY, ASSEM G · 2011 to 2014
$1.5M
NHLBI NIH HHS R01 HL109362NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

Evidence suggests that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, may reduce the risk of Alzheimer's disease (AD). Statin action in patients with AD, as in those with heart disease, is likely to be at least partly independent of the effects of statins on cholesterol. Statins can alter cellular signaling and protein trafficking through inhibition of isoprenylation of Rho, Cdc42, and Rab family GTPases. The effects of statins on protein isoprenylation in vivo, particularly in the central nervous system, are poorly studied. We utilized two-dimensional gel electrophoresis approaches to directly monitor the levels of isoprenylated and non-isoprenylated forms of Rho and Rab family GTPases. We report that simvastatin significantly inhibits RhoA and Rab4, and Rab6 isoprenylation at doses as low as 50nM in vitro. We also provide the first in vivo evidence that statins inhibit the isoprenylation of RhoA in the brains of rats and RhoA, Cdc42, and H-Ras in the brains of mice treated with clinically relevant doses of simvastatin.

Indexed as

AnimalsBlotting, WesternBraincdc42 GTP-Binding ProteinCell Line, TumorCentral Nervous System AgentsDrug Evaluation, PreclinicalElectrophoresis, Gel, Two-DimensionalHydroxymethylglutaryl-CoA Reductase InhibitorsIsoelectric FocusingMice, Inbred C57BLProtein PrenylationProto-Oncogene Proteins p21(ras)Rats, Inbred SHRrhoA GTP-Binding ProteinSimvastatincdc42 GTP-Binding ProteinCdc42 protein, mouseCentral Nervous System AgentsHras protein, mouseHydroxymethylglutaryl-CoA Reductase InhibitorsProto-Oncogene Proteins p21(ras)rhoA GTP-Binding ProteinSimvastatinAlzheimer’s diseaseCdc42isoprenylationRabRhoAsimvastatin

Identifiers

PMID27180285
PMCPMC4905803
OpenAlexW2349572554

What OpenQuestion 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 OpenQuestion graph.