Evidence map›Paper›PMID 25453074›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Multiple functional therapeutic effects of the estrogen receptor β agonist indazole-Cl in a mouse model of multiple sclerosis.

Spencer M Moore, Anna J Khalaj, Shalini Kumar, Zachary Winchester, JaeHee Yoon, Timothy Yoo, Leonardo Martinez-Torres, Norio Yasui, John A Katzenellenbogen, Seema Kaushalya Tiwari-Woodruff

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
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  5. Article
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  7. Review
  8. Review
  9. Article
  10. Nuclear hormone receptors in demyelinating diseases.Journal of neuroendocrinology · 2022
    Review
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  18. Aberrant ER Stress Induced Neuronal-IFNβ Elicits White Matter Injury Due to Microglial Activation and T-Cell Infiltration after TBI.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  19. Review
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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

10 authors at 3 institutions in 1 country.

Spencer M MooreDepartment of Neurology.ORCID http://orcid.org/0000-0001-9811-9007
Anna J KhalajDepartment of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521;
Shalini KumarIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience at the School of Medicine, University of California, Los Angeles, CA 90095; and.
Zachary WinchesterDepartment of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521;
JaeHee YoonDepartment of Neurology.
Timothy YooDepartment of Neurology.
Leonardo Martinez-TorresDepartment of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521;
Norio YasuiDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
John A KatzenellenbogenDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Seema Kaushalya Tiwari-WoodruffDepartment of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience at the School of Medicine, University of California, Los Angeles, CA 90095; and Brain Research Institute, and seema.tiwari-woodruff@ucr.edu.
University of California, Riverside · USUniversity of Illinois Urbana-Champaign · USIntel (United States) · US

Funding

Novel Ligands and Mechanisms to Achieve Selective Nuclear Receptor ActivityR01DK015556 · NIDDK · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI KATZENELLENBOGEN, JOHN A. · 1986 to 2016
$1.6M
Stimulating oligodendrocyte progenitor cell differentiation and remyelinationR01NS081141 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI TIWARI-WOODRUFF, SEEMA K · 2014 to 2017
$1.3M
Estrogen receptor B ligand: A novel treatment to enhance functional remyelinationR21NS075198 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIWARI-WOODRUFF, SEEMA K · 2011 to 2012
$424k
NIDDK NIH HHS R01 DK015556NIDDK NIH HHS R01DK015556NINDS NIH HHS R01 NS081141NINDS NIH HHS R01-NS081141-01A1NINDS NIH HHS R21 NS075198NINDS NIH HHS R21NS075198
6 · The paper itself

Abstract

Currently available immunomodulatory therapies do not stop the pathogenesis underlying multiple sclerosis (MS) and are only partially effective in preventing the onset of permanent disability in patients with MS. Identifying a drug that stimulates endogenous remyelination and/or minimizes axonal degeneration would reduce the rate and degree of disease progression. Here, the effects of the highly selective estrogen receptor (ER) β agonist indazole chloride (Ind-Cl) on functional remyelination in chronic experimental autoimmune encephalomyelitis (EAE) mice were investigated by assessing pathologic, functional, and behavioral consequences of both prophylactic and therapeutic (peak EAE) treatment with Ind-Cl. Peripheral cytokines from autoantigen-stimulated splenocytes were measured, and central nervous system infiltration by immune cells, axon health, and myelination were assessed by immunohistochemistry and electron microscopy. Therapeutic Ind-Cl improved clinical disease and rotorod performance and also decreased peripheral Th1 cytokines and reactive astrocytes, activated microglia, and T cells in brains of EAE mice. Increased callosal myelination and mature oligodendrocytes correlated with improved callosal conduction and refractoriness. Therapeutic Ind-Cl-induced remyelination was independent of its effects on the immune system, as Ind-Cl increased remyelination within the cuprizone diet-induced demyelinating model. We conclude that Ind-Cl is a refined pharmacologic agent capable of stimulating functionally relevant endogenous myelination, with important implications for progressive MS treatment.

Indexed as

Analysis of VarianceAnimalsBlotting, WesternEncephalomyelitis, Autoimmune, ExperimentalEstrogen Receptor betaFemaleHydrocarbons, ChlorinatedImmunohistochemistryImmunologic FactorsIndazolesMaleMiceMice, Inbred C57BLMotor SkillsMyelin SheathRotarod Performance TestEstrogen Receptor betaHydrocarbons, ChlorinatedImmunologic FactorsIndazolescuprizone dietexperimental autoimmune encephalomyelitismotor deficitPI3/Akt/mTORremyelination

Identifiers

PMID25453074
PMCPMC4273334
OpenAlexW2019476809

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.