ArticleJournal of immunology (Baltimore, Md. : 1950)2002
Inhibition of Rho GTPases with protein prenyltransferase inhibitors prevents leukocyte recruitment to the central nervous system and attenuates clinical signs of disease in an animal model of multiple sclerosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03896217 (A Double-blind, Randomised, Placebo-controlled Single-site Study of High Dose Simvastatin Treatment for Secondary Progressive Multiple Sclerosis), which is not on this map. Cited by 44 papers.
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.
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.
A Double-blind, Randomised, Placebo-controlled Single-site Study of High Dose Simvastatin Treatment for Secondary Progressive Multiple Sclerosis: Impact on Vascular Perfusion and Oxidative Damage
Who cites it
44 citing papers in PubMed, 114 citations in OpenAlex.
- Pyrin inflammasome-driven erosive arthritis caused by unprenylated RHO GTPase signaling.EMBO molecular medicine · 2025Article
- Protein Prenylation in Plants: Mechanisms and Functional Implications.Plants (Basel, Switzerland) · 2025Review
- Unsupervised Machine Learning Revealed that Repeat Transcranial Magnetic Stimulation is More Suitable for Stroke Patients with Statin.Neurology and therapy · 2024Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains.Frontiers in neurology · 2021Article
- Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions.Nature communications · 2019Article
- New tricks for human farnesyltransferase inhibitor: cancer and beyond.MedChemComm · 2017Review
- Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Role of Geranylgeranyltransferase I-Mediated Protein Prenylation in the Brain.Molecular neurobiology · 2016Review
- Selective Gas-Phase Oxidation and Localization of Alkylated Cysteine Residues in Polypeptide Ions via Ion/Ion Chemistry.Journal of proteome research · 2016Article
- Recent insights into endothelial control of leukocyte extravasation.Cellular and molecular life sciences : CMLS · 2016Review
- Protein prenylation: enzymes, therapeutics, and biotechnology applications.ACS chemical biology · 2015Review
- Cholesterol 24S-Hydroxylase Overexpression Inhibits the Liver X Receptor (LXR) Pathway by Activating Small Guanosine Triphosphate-Binding Proteins (sGTPases) in Neuronal Cells.Molecular neurobiology · 2015Article
- Rho kinase as a target for cerebral vascular disorders.Future medicinal chemistry · 2015Review
- Amelioration of cisplatin-induced experimental peripheral neuropathy by a small molecule targeting p75 NTR.Neurotoxicology · 2014Article
- Axon growth inhibition by RhoA/ROCK in the central nervous system.Frontiers in neuroscience · 2014Review
- Novel role of Cdc42 and RalA GTPases in TNF-α mediated secretion of CCL2.Small GTPases · 2014Article
- Prenyltransferase Inhibitors: Treating Human Ailments from Cancer to Parasitic Infections.MedChemComm · 2013Article
- Statin use and ocular inflammatory disease risk.Journal of ophthalmic inflammation and infection · 2013Article
- Streptococcal m1 protein triggers farnesyltransferase-dependent formation of CXC chemokines in alveolar macrophages and neutrophil infiltration of the lungs.Infection and immunity · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
The ICAM-1-mediated brain endothelial cell (EC)-signaling pathway induced by adherent lymphocytes is a central element in facilitating lymphocyte migration through the tight endothelial barrier of the brain. Rho proteins, which must undergo posttranslational prenylation to be functionally active, have been shown to be an essential component of this signaling cascade. In this study, we have evaluated the effect of inhibiting protein prenylation in brain ECs on their ability to support T lymphocyte migration. ECs treated in vitro with protein prenylation inhibitors resulted in a significant reduction in transendothelial T lymphocyte migration. To determine the therapeutic potential of this approach, an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis, was induced in Biozzi ABH mice. Animals treated before disease onset with protein prenylation inhibitors exhibited a dramatic and significant reduction in both leukocyte infiltration into the CNS and clinical presentation of disease compared with untreated animals. These studies demonstrate, for the first time, the potential for pharmacologically targeting CNS EC signaling responses, and particularly endothelial Rho proteins, as a means of attenuating leukocyte recruitment to the CNS.
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Registered trials
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.