Evidence map›Paper›PMID 26627258›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Proline-, glutamic acid-, and leucine-rich protein 1 mediates estrogen rapid signaling and neuroprotection in the brain.

Gangadhara R Sareddy, Quanguang Zhang, Ruimin Wang, Erin Scott, Yi Zou, Jason C O'Connor, Yidong Chen, Yan Dong, Ratna K Vadlamudi, Darrell Brann

Open access · bronzeAbstract 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, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Astrocyte-Derived Estrogen Regulates Reactive Astrogliosis and is Neuroprotective following Ischemic Brain Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  5. Neuron-Derived Estrogen Is Critical for Astrocyte Activation and Neuroprotection of the Ischemic Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. 17Oxidative medicine and cellular longevity · 2018
    Article
  16. Article
  17. Article
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  19. Article
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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 5 institutions in 2 countries.

Gangadhara R SareddyDepartment of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229;
Quanguang ZhangDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912;
Ruimin WangDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912; Neurobiology Institute of Medical Research Center, North China University of Science and Technology, Tangshan, People's Republic of China 063000;
Erin ScottDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912;
Yi ZouDepartment of Epidemiology & Biostatistics, University of Texas Health Science Center, San Antonio, TX 78229;
Jason C O'ConnorDepartment of Pharmacology, University of Texas Health Science Center, San Antonio, TX 78229; South Texas Veterans Health System, Audie L. Murphy VA Hospital, San Antonio, TX 78229;
Yidong ChenDepartment of Epidemiology & Biostatistics, University of Texas Health Science Center, San Antonio, TX 78229;
Yan DongDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912;
Ratna K VadlamudiDepartment of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229; dbrann@gru.edu vadlamudi@uthscsa.edu.
Darrell BrannDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912; Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904 dbrann@gru.edu vadlamudi@uthscsa.edu.
The University of Texas Health Science Center at San Antonio · USAugusta University · USAudie L. Murphy Memorial VA Hospital · USCharlie Norwood VA Medical Center · USNorth China University of Science and Technology · CN

Funding

Neuroprotective and Neurogenic Actions of E2 and SERMsR01NS050730 · NINDS · MEDICAL COLLEGE OF GEORGIA (MCG) · PI BRANN, DARRELL W, VADLAMUDI, RATNA K · 2005 to 2014
$3.2M
Biobehavioral Role of Brain Kynurenine Metabolism in Mental IllnessR01MH090127 · NIMH · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI O'CONNOR, JASON C · 2010 to 2014
$1.8M
NINDS NIH HHS NS050730NINDS NIH HHS R01 NS050730
6 · The paper itself

Abstract

17-β estradiol (E2) has been implicated as neuroprotective in a variety of neurodegenerative disorders. However, the underlying mechanism remains unknown. Here, we provide genetic evidence, using forebrain-specific knockout (FBKO) mice, that proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), an estrogen receptor coregulator protein, is essential for the extranuclear signaling and neuroprotective actions of E2 in the hippocampal CA1 region after global cerebral ischemia (GCI). E2-mediated extranuclear signaling (including activation of extracellular signal-regulated kinase and Akt) and antiapoptotic effects [such as attenuation of JNK signaling and increase in phosphorylation of glycogen synthase kinase-3β (GSK3β)] after GCI were compromised in PELP1 FBKO mice. Mechanistic studies revealed that PELP1 interacts with GSK3β, E2 modulates interaction of PELP1 with GSK3β, and PELP1 is a novel substrate for GSK3β. RNA-seq analysis of control and PELP1 FBKO mice after ischemia demonstrated alterations in several genes related to inflammation, metabolism, and survival in PELP1 FBKO mice, as well as a significant reduction in the activation of the Wnt/β-catenin signaling pathway. In addition, PELP1 FBKO studies revealed that PELP1 is required for E2-mediated neuroprotection and for E2-mediated preservation of cognitive function after GCI. Collectively, our data provide the first direct in vivo evidence, to our knowledge, of an essential role for PELP1 in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain.

Indexed as

AnimalsBrain IschemiaCA1 Region, HippocampalCognitionCSK Tyrosine-Protein KinaseEstrogen Receptor alphaEstrogensFemaleGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHomeodomain ProteinsInflammationMaleMaze LearningMiceMice, Inbred C57BLCSK Tyrosine-Protein KinaseEstrogen Receptor alphaEstrogensGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, mouseHmx3 protein, mouseHomeodomain ProteinsNerve Tissue ProteinsOligonucleotides, Antisensesrc-Family Kinases17-β estradiolcognitionextranuclearneuroprotectionPELP1

Identifiers

PMID26627258
PMCPMC4672783
OpenAlexW2180920467

What OpenQuestion holds

Textmetadata
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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.